STURGE WEBER SYNDROME

 

INTRODUCTION:

Sturge-Weber syndrome (SWS), also known as encephalotrigeminal angiomatosis, is one of the common phakomatoses.

 

It is a neuro-cutaneous disorder with angiomas involving the leptomeninges (leptomeningeal angiomas) and the skin of the face, especially in the distribution of the ophthalmic (V1) and maxillary (V2) nerves. It is characterized by the aforementioned cutaneous angiomas (known as port-wine stain or nevus flemmeus; a type of capillary hemangioma), glaucoma, seizures, intellectual disability and ipsilateral leptomeningeal angioma. Classically, SWS is characterized by the triad of port-wine stain, leptomeningeal hemangioma and ocular hemangioma.

The condition was first reported by Schirmer in 1860, and later described by Sturge in 1897 and by Weber in 1922.

A useful mnemonic to remember the features of SWS is STURGE.

 

The nervous system involvement frequently causes seizure disorders, hemispheric motor or sensory defects, and intellectual deficiency. A characteristic radiographic finding is cortical calcifications that develop after several years and appear as double densities or “railroad tracks.”

 

The angiomata are present at birth and are usually unilateral, although bilateral cases also occur. 

 

In one review of 51 patients, the condition was recognized before 24 months of age in more than half the cases. Unlike other phakomatoses, SWS is not hereditary. It has been reported in 1 per 50,000 live births, without any sex or racial predilection.

A mutation in the GNAQ gene has been implicated in the development of SWS. The embryologic basis of SWS has been reported to be related to an impaired development of the cell precursors in the neural crest during the first embryological trimester, leading to the characteristic malformations observed in the central nervous system, skin, and eyes.

According to the clinical manifestations, SWS is classified into four types: 1) presence of brain and facial angioma, with or without glaucoma, 2) PWS without brain involvement, with or without glaucoma, 3) isolated brain angioma, usually without glaucoma, and 4) type 1 and associated with systemic manifestation such as tuberous sclerosis. 

 

Slitlamp examination typically reveals a dense episcleral vascular plexus and occasional ampulliform dilatations of conjunctival vessels. These findings are on the side of the cutaneous lesion. Some patients also have a choroidal hemangioma. 

 

In view of multiple organs being involved in SWS, a multidisciplinary approach is recommended to deliver comprehensive care and optimize overall outcomes.

MECHANISM OF GLAUCOMA:

 Glaucoma occurs in 30-70% of patients with SWS. This condition appears to have the highest incidence of glaucoma among all systemic hamartosis. About 60% patients present with glaucoma at birth and the rest manifest glaucoma in later life. The incidence of glaucoma increases when the PWS involves the eyelid and occurs ipsilateral to the port-wine stain. Glaucoma in SWS patients shows a bimodal peak of age development: an early-onset (congenital) form affecting ~60% of patients and a later-onset form during childhood and ado­lescence (40% of cases).

The pathogenesis of glaucoma in the Sturge-Weber syndrome has been a controversial issue.

The main theories on the mechanism of glaucoma in SWS include the following:

1) Weiss described two mechanisms, the more common of which occurs in infants, with a developmental anomaly of the anterior chamber angle similar to that of congenital glaucoma. One histopathologic report described a partial developmental anomaly of the anterior chamber angle, and another study revealed neovascularization in the trabecular meshwork.

The other mechanism of glaucoma appears later in life and is associated with an open anterior chamber angle and small arteriovenous fistulas in the episcleral vessels.

The mechanical mechanism related to congenital malforma­tion of the anterior chamber angle explains glaucoma on the basis of increased resistance to aqueous humor outflow: in this case, the iris does not have the flat anterior insertion characteristic of the congenital form.

2) Phelps observed episcleral hemangiomas in all cases of SWS and elevated episcleral venous pressure (EVP). According to him, elevated EVP is the most common glaucoma mechanism in all ages of patients with the SWS.

The increase in EVP due to arteriovenous shunts into the episcleral hemangioma causes elevated IOP. This theory is based on the observation of a normal angle structure, blood within Schlemm’s canal, and more severe glaucoma.

3) Fluid hypersecretion by either the ciliary body or the choroidal hemangioma is also suspected to cause increased IOP.

4) Another theory points to the abnormal hemodynamics of the episclera and the anterior chamber angle due to premature aging of the trabecular meshwork–Schlemm’s canal complex, as observed in SWS later-onset glaucoma.

5) Yet another mechanism of glaucoma is due to development of neovascularization as a consequence of ocular ischemia. Subsequently, peripheral anterior synechiae may develop and result in secondary angle closure glaucoma.

MANAGEMENT:

Early-onset glaucoma in SWS is complex due to the anatomical peculiarities and resistance to therapy. Most of these eyes require surgical intervention in the form of goniotomy or trabeculectomy. However, the outcomes are generally worse than those observed with primary congenital glaucoma, and these cases often require additional surgery with trabeculectomy or a glaucoma drainage device.

For late onset glaucoma, medical therapy is initiated first; aqueous suppressants and miotics tend to be the most successful. Prostaglandin analogues have been reported to have inconsistent response rates. Although in one study nearly 50% patients were effective on Latanoprost treatment, at one year of follow-up. However, long term use of PGIs has a risk of uveal effusion. As most of the agents do not address the issue of raised EVP, agents targeting that mechanism should be investigated.

In cases unresponsive to medical therapy, trabeculectomy is the procedure of choice, as it bypasses the episcleral venous system. Augmentation with anti-metabolites tend to improve outcomes of trabeculectomy. It should be noted that trabeculectomy is associated with a much higher risk of choroidal effusions or suprachoroidal hemorrhages in eyes with SWS.

Glaucoma drainage devices are another effective option for glaucoma secondary to SWS. Hamush et al. implanted Ahmed glaucoma drainage device in 11 eyes. The cumulative probability of success was 79% at 24 months, 59% at 42 months, and 30% at 60 months. Another study of 10 patients implanted with the Baerveldt valve reported successful outcome in 100% patients. Reports of short term effectiveness of ExPress shunt are also published.

Cyclophotocoagulation is another option in patients with refractory glaucoma or in patients who are likely to have much higher risk of intraoperative or postoperative complications (choroidal expulsive hemorrhage or choroidal detachment) after glaucoma filtration surgery. In a study of 10 eyes which underwent the procedure, 62.5% had adequate control of IOP.

PROGNOSIS:

Patients with SWS have a lower life expectancy compared to the general population. In cases where the leptomeningeal lesions are bilateral, patients usually have more severe neurological manifestations and a worse prognosis.