Continuing Education Activity

Wyburn-Mason syndrome is a rare nonhereditary congenital phakomatoses which presents with multiple arteriovenous malformations that tend to be large and predominantly affect the brain, eye, and facial structures. This activity outlines the evaluation and management of patients presenting with Wyburn-Mason syndrome and highlights the role of the interprofessional team in managing the patients with this condition.

Objectives:

• Outline the range of neurological symptoms that may be present in patients with Wyburn-Mason syndrome.
• Review the treatment options for arteriovenous malformations in patients with Wyburn-Mason syndrome.
• Describe the pathophysiology of Wyburn-Mason syndrome.
• Explain the importance of collaboration and coordination among the interprofessional team members to improve outcomes for patients affected by Wyburn-Mason syndrome.

Introduction

Wyburn-Mason syndrome (WMS), also known as racemose angioma, is a congenital nonhereditary neurocutaneous syndrome or phakomatoses that presents with multiple arteriovenous malformations (AVM). WMS has varied phenotypical expressions but predominantly affects the face and brain. Bonnet, Dechaume, and Blanc were first to recognize AVM of face, retina, and brain in the year 1937 and Wyburn-Mason described in detail about this disease in 1943.[1] In recognition of these authors, this disease is referred to as Bonnet-Dechaume-Blanc syndrome or Wyburn-Mason syndrome. 

The AVM range in size but often tend to be large. When involving the brain, these AVM tend to localize to the midbrain region, thus necessitating neurologic imaging to rule out life-threatening or potentially debilitating lesions in this area. The ophthalmoscopic presentation of the AVM in WMS is characteristic with dilated and tortuous vessels present over the optic disc and extending variably to the retinal periphery.  Presenting vision may range from normal to no light perception and depends upon the associated ophthalmic complications. Vascular malformations may be present elsewhere in the body. Wyburn-Mason syndrome does not cause significant cutaneous manifestations, except for the rare occurrence of small facial angioma over the trigeminal region of the face.[2][3][4][5][1][5]

Etiology

Wyburn-Mason syndrome is a congenital, nonhereditary, sporadic disorder. The precise risk factors associated with this condition are presently unknown and some anomaly in the organogenesis is explained to be the etiology. An embryonic defect is believed to result in the spread of vascular lesions from the cephalic origin along the route of migration before the actual migration of the vascular cells to their final destination. The concept of cerebrofacial arteriovenous metameric syndrome (CAMS) is a classification system that describes the spectrum of phenotypical expression of AVM in the cerebral, orbital, and facial region. There are 3 types of CAMS. CAMS1 involves corpus callosum, hypothalamus, olfactory tract, forehead, and nose. CAMS2 involves cortex and diencephalon, optic chiasma, optic nerve, retina, sphenoid, maxilla, and cheek. Wyburn-Mason syndrome has been named as CAMS2 according to this system of classification. CAMS3 involves the cerebellum, temporal bone, and mandible. [5][6][7][8][1][8]

Epidemiology

Wyburn-Mason is extremely uncommon and less than 100 cases have been reported in the literature. There is no known gender or racial predilection. It is estimated that 30% of the patients with the retinal findings have brain findings and 8% of the patients with brain findings have retinal findings. [1]

Large retinal arteriovenous malformations, which cause visual or neurologic impairment usually are diagnosed in early life. Smaller arteriovenous malformations may remain asymptomatic or be diagnosed only in later life.

Pathophysiology

AVM in WMS is typically in the midbrain and ipsilateral retina. Vision loss from Wyburn-Mason syndrome occurs secondary to the presence and location of the arteriovenous malformations in the retina or the orbit. The tortuosity of AVM may increase over time which can cause obscuration of the visual centers, choroidal infarctions, retina ischemia, or by causing compression of the optic nerve or retinal vascular occlusions. These high-flow arteriovenous malformations usually do not bleed or cause exudation in the retina. However, intracranial AVMs can bleed. [9] Sometimes, there can be exudation and edema associated with retinal AVM. The proposed mechanisms of this edema include leakage from capillaries near the AVMs and pressure changes along the capillaries.[10][11]

History and Physical

Wyburn-Mason syndrome presents with a range of neurological symptoms that primarily depend on the location and size of the arteriovenous malformations. Neurological symptoms may include seizures, headaches, hemiparesis, visual deficits, cranial neuropathies, and hydrocephalus. [1] Arteriovenous malformations located outside the central nervous system (CNS) may present with hematuria, hemoptysis, epistaxis, or frank bleeding. WMS usually affects one eye, though bilateral involvement has been infrequently reported.[2] Small arteriovenous malformations within the eye may cause no visual symptoms. Large arteriovenous malformations can produce severe vision loss. Eye problems can include blepharoptosis, proptosis, ocular motility disorders, retinal hemorrhages, vitreous hemorrhages, retinal detachments, vein occlusions (which can be complicated by associated rubeosis iridis and secondary glaucoma), optic disc edema, and optic atrophy. Orbital AVMs can present with pulsatile proptosis and can have an accompanying bruit.

The majority of individuals have involvement of the eye at a young age and can be severely visually impaired. If the arteriovenous malformations are diagnosed at an early age, the risk of systemic involvement is high.

Evaluation

The diagnosis of Wyburn-Mason syndrome is made on clinical examination. Retinal arteriovenous malformations are usually diagnosed by ophthalmoscopy although fluorescein angiography may be required to demonstrate smaller lesions. Most arteriovenous malformations do not leak on angiography. Ultrasound and optical coherence tomography (OCT) can also confirm the diagnosis and be used to follow changes in the nerve fiber layer, macula, and retina over time. OCT is very useful for the diagnosis of associated macular edema and serous retinal detachment. Exophthalmometry is needed for the grading of proptosis if proptosis is present. Intracranial arteriovenous malformations can be diagnosed with computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), or cerebral arteriography. Catheter angiography can demonstrate the size, location, and characteristics of the feeding arteries and draining veins and is felt to be the best method to analyze the exact angioarchitecture of the lesion. Lesions have been reported in the skin but are very uncommon. CNS vascular lesions are typically on the same side as the involved eye. Central nervous system vascular lesions often involve the midbrain.

Treatment / Management

Once there is a diagnosis of Wyburn-Mason syndrome, the treatment is based on the location of the arteriovenous malformations and the corresponding symptoms. Unruptured arteriovenous malformations without symptoms should be observed. Other options include radiation therapy, embolization, surgical resection, or a combination of these approaches. Intracranial AVM s should be approached as if it is having a risk of rupture of 2.2% per year. [12] Since intracranial surgeries are having increased risk of complications, observation and conservative management are advised in patients having mild symptoms e.g mild proptosis or mild ptosis.

Most retinal arteriovenous malformations do not bleed externally but can produce minute hemorrhages that affect vision. Because of the stability of retinal lesions, ophthalmologists often serve to mainly diagnose Wyburn-Mason, obtain neuroimaging, organize systemic referrals, and perform periodic ophthalmologic assessments. However, complications arising from retinal AVMs need treatment. Patients who develop neovascular glaucoma require retinal photocoagulation to treat retinal ischemia. Pars plana vitrectomy may be done for non-clearing vitreous hemorrhage, and cyclodestructive procedures may be required to treat painful blind eyes with raised intraocular pressure resulting form neovascular glaucoma.[13][14] Macular edema has been successfully managed with intravitreal injection of anti-VEGF agents in recent times. [2][14]

Differential Diagnosis

The differential diagnosis of WMS includes Von Hippel Lindau syndrome, vasoproliferative tumors (VPT), Sturge Weber syndrome, and retinal cavernous hemangioma.

Von Hippel-Lindau disease is associated with retinal capillary hemangioma (RCH), cerebral aneurysm, renal cell carcinoma, pheochromocytoma, and thus, should be considered as a differential diagnosis to decrease the risk of complications including the risk of death. Clinically RCH appears as a round, circumscribed, orange to a red retinal lesion in the peripapillary or peripheral location. The RCH is associated with a prominent feeder vessel. [9] Abdominal radiological tests need to evaluate the kidneys. VHL is inherited in an autosomal dominant fashion, unlike WMS which is nonhereditary.

Vasoproliferative tumor is characterized by retinal nodules composed of glial cells interlaced with a fine capillary network and dilated hyalinised blood vessels. [15] VPT can be primary or secondary to retinal conditions like retinitis pigmentosa, coat’s disease, and post-vitreoretinal surgery. Cryotherapy is used for exudative retinal detachment in VPT. [15]

Sturge-Weber syndrome should be considered if there are port-wine stains (facial angioma) or ipsilateral juvenile or congenital open-angle glaucoma. Hemangiomas of the meninges are found in Sturge-Weber syndrome.

Retinal cavernous hemangioma appears as a dark grape-like cluster of venous intraretinal aneurysms. The characteristic FFA finding is hypofluorescence till the late phase with a slow nonleaking filling of the aneurysms. [9] 

Staging

Archer et al. classified retinal arteriovenous malformations into 3 groups:[16] 

• Group 1 consists of retinal AVM consisting of a major artery and vein with an abnormal capillary network. These are small arteriole-venule anastomoses which can be subtle and difficult to detect clinically. These are stationary and rarely cause visual symptoms.

• Group 2 consists of retinal AVM between an artery and vein without a capillary network with the marked hyperdynamic flow in between the AVM. Vision may be affected if macular edema or hemorrhage resulting from the breakdown of blood-retinal barrier or venous thrombosis.

• Group 3 consists of markedly convoluted, dilated, tortuous retinal vessels without a capillary network in between and presence of retinal disorganization. It can be nearly impossible to separate arteries from veins. These eyes usually have severe vision loss and more likely to have intracranial malformations. These patients are usually diagnosed in childhood, and they have a higher risk of systemic vascular involvement.

Prognosis

The natural history of WMS is unknown and the management is controversial. Hence, the prognosis of WMS is uncertain.

Patients of WMS may remain asymptomatic both visually and systemically. However, the prognosis of visually symptomatic patients depends upon the complications causing visual symptoms. Macular edema due to exudation from the AVM can be managed with intravitreal-anti-VEGF injections. Nonclearing VH can be managed with pars plana vitrectomy. Neovascular glaucoma can be managed with retinal photocoagulation and pressure-lowering therapies. However, the prognosis remains guarded mostly. 

The involvement of maxillofacial or mandibular vessels can lead to excessive hemorrhages during dental procedures. The treating dentist or surgeon should be aware of this potential complication.

Intracranial surgeries for AVM remains largely controversial. A few reports of good outcome has been mentioned in patients with intracranial hemorrhage due to AVM.[17] [18] However, surgical resection of AVM located in the suprasellar and chiasmal location may place the vision and visual field in jeopardy.[19] [20]

Many surgeons opt to treat these intracranial AVMs conservatively. [20] [17]

Complications

Complications related to AVM can be intracranial hemorrhage or mechanical pressure-related damage. Ophthalmic complications include exudation from the AVM causing macular edema, retinal ischemia, retinal vein occlusion, neovascular glaucoma, and vitreous hemorrhage.

The complications related to intracranial surgery include loss of vision or field of vision.

Complications of dental or maxillary surgical procedures may include profuse bleeding due to the presence of these AVM. 

Deterrence and Patient Education

The patients of WMS should be explained about the periodic check-up to rule out any early complications of the AVM.

Intracranial surgeries should be a reserved option for a few patients only e.g those with hemorrhage due to AVM or severe vision loss in one eye. [18] Intracranial surgeries are better to be avoided in asymptomatic and minimally symptomatic patients. 

Enhancing Healthcare Team Outcomes

Once there is a diagnosis of Wyburn-Mason syndrome, the treatment is based on the location of the arteriovenous malformations and the corresponding symptoms. Because the condition is associated with high morbidity and mortality linked to hemorrhage, the disorder is best managed by an interprofessional team that includes an internist, geneticist, hematologist, radiologist, ophthalmologist, neurosurgeon, and intensivist. Dental surgeons and otorhinolaryngologists should be cautioned about the increased risk of hemorrhage for any interventional procedure that they plan to do. Even during simple tooth extraction, significant hemorrhage can occur. Follow up is usually done by the primary care provider and nurse practitioner.  Patients with unruptured arteriovenous malformations without symptoms can be observed; other options include radiation therapy, embolization, surgical resection, or a combination of these approaches. Before the patient undergoes any invasive procedure, the healthcare professional should be familiar with the syndrome and how to manage the hemorrhage. The outcomes for patients with eye involvement are guarded; most patients do end up with some degree of vision loss.[21] (Level V)