Sturge-Weber Syndrome (SWS), also known as encephalotrigeminal angiomatosis, is a congenital neuro-oculocutaneous syndrome that presents at birth.
[1]
SWS was first reported by Dr. Schirmer in 1860 with later descriptions by Dr. Sturge in 1897 and Dr. Weber in 1922.
[2]
It is characterized as a part of the neuroectodermal dysplasias, also known as phakomatoses. Unlike other phakomatoses, SWS is not hereditary. The incidence has been reported to be 1 per 50,000 live births and, no racial or sex predilection has been found.
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SWS can be classified as trisymptomatic when the skin, eye, and central nervous system (CNS) are affected; bisymptomatic when the skin and CNS or the skin and eye are affected; and monosymptomatic when the skin or the CNS is affected.
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The typical triad consists of facial capillary malformation (port wine stain or nevus flammeus), an ipsilateral vascular anomaly in the brain (leptomeningeal hemangioma), and ocular hemangioma.
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The most common type of vascular malformation is port wine stain (PWS), with an overall incidence of 0.3% in live births.
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The incidence of SWS in patients with a PWS has been reported to be between
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and 5%.
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A PWS is a well delineated red macule that is present at birth and gets darker and thicker with age. In addition, many small and large dark nodules can grow on the surface, resembling pyogenic granulomas.
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The PWS is typically present in the V1 and V2 distributions of the trigeminal nerve. Leptomeningeal and ocular hemangiomas are usually accompanied by PWS in the eyelids, with the upper eyelid being more frequently affected than the lower.
[14]
If the PWS is present bilaterally, the likelihood of having SWS is higher than when the PWS is present unilaterally. In some cases, the ipsilateral nasal and buccal mucosa may also be involved on the side of PWS.
The distribution of PWS along various branches of the trigmenial nerve determines the severity of associated neurological deficits and associated glaucoma. Hennedige et al.
[8]
reported that patients with PWS only in the V1 dermatome had a 6.7% risk of glaucoma and 26.7% risk of neurologic manifestations. They reported no risk of glaucoma and a lower risk of neurologic manifestations, 3.1%, when only the V2 distribution was involved. When both the V1 and V2 dermatomes were involved, the risk of both glaucoma (31.8%) and neurologic manifestations (54.5%) was much higher.
[8]
They also observed that, if all three dermatomes (V1, V2, V3) were involved, the risk of neurologic manifestations quadrupled.
The PWS has been reported to improve with pulsed dye laser photocoagulation.
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This laser uses thermolysis and results in irreversible damage to blood vessels but spares other components of the skin.
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Often, multiple treatments are required with minimal to no side effects. However, the patients rarely get a 100% clearance of their skin discoloration.
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Central forehead stains have a better outcome than do central facial stains.
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The patients with V2 involvement tend to have the worst outcome after laser treatment. By the fifth decade of life, approximately 65% of patients will have hypertrophy and nodules within the lesions. Therefore, many psychological benefits have been reported after the laser treatment of PWS.
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Neurologic Manifestations and Treatment
The most common neurological manifestation in SWS is seizures, with partial seizures being the most common type. Seizures are present in approximately 80% of patients and usually develop during the first year of life. The seizures will manifest before the first year of age in 75% of the patients, although some patients may experience seizures for the first time as adults. Seizures will be present in 95% of patients with bilateral leptomeningeal lesions and 75% of patients with unilateral lesions.
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Bilateral lesions present in 7% to 26% of cases and are usually accompanied by more severe neurological symptoms compared to unilateral lesions.
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There is also an association between earlier onset of seizures and the development of other neurological manifestations such as contralateral hemiparesis, hemianopsia, hemiplegia, mental retardation, developmental delay, or behavioral problems.
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[28]
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Developmental delay, mental retardation, and headaches occur in approximately 50% of patients with SWS.
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In addition, approximately 30% of patients will be severely mentally handicapped.
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However, patients with no seizures before 2 years of age will have normal intelligence and development.
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The leptomeningeal lesions are present at birth and usually located in the occipital and parietal lobes of the meninges.8 These can be detected by magnetic resonance imaging or computed tomography.
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Even though computed tomography is very effective in detecting intracranial calcifications, these are usually not present in neonates. Therefore, the best method to diagnose the leptomeningeal lesions is magnetic resonance imaging with gadolinium contrast.
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The most important aspect in the treatment of SWS is seizure control. Management of seizures with anticonvulsant therapy has been reported to have favorable results in approximately half of the patients with SWS. Nevertheless, the majority of patients will require more than one medication for treatment.
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In cases where seizures cannot be managed with medical therapy, surgical therapy may be beneficial.
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When seizures are poorly controlled and are present in only one hemisphere, hemispherectomy has been reported to have favorable results, with approximately 80% of the patients being seizure free after the procedure.
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Ocular Manifestations and Treatment
Ocular manifestations of SWS include conjunctival, episcleral, and choroidal hemangiomas. Choroidal hemangiomas may be present in up to 71% of patients with SWS and may be circumscribed or diffuse.
[4]
SWS is usually associated with the diffuse variant that often presents in patients with late-onset glaucoma.
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The treatment of patients with glaucoma and diffuse choroidal hemangiomas is extremely challenging and may be associated with devastating complications, such as choroidal effusions, retinal detachments, or severe hemorrhages. Since these patients are usually refractory to medical therapy, other treatment options have been used. These include radiotherapy, stereotactic radiotherapy, plaque radiotherapy, proton beam, anti-vascular endothelial growth factors, and photodynamic therapy.
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Glaucoma is one of the most challenging ocular manifestations of SWS.
Glaucoma
Glaucoma presents in 30-70% of patients with SWS.
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Of the systemic hamartosis, SWS has the highest incidence of glaucoma. Approximately 60% of patients present with glaucoma at birth and 40% manifest glaucoma later in life.
[46]
The incidence of glaucoma increases when the PWS involves the eyelid.
[47]
It presents most often ipsilateral to the PWS but can also manifest bilaterally.
[48]
The two main mechanisms of glaucoma in SWS are malformation of the anterior chamber angle and an elevated episcleral venous pressure.
[49]
An abnormal anterior chamber angle has been demonstrated in enucleated eyes with SWS.
[50]
The abnormalities of the anterior chamber angle in patients with SWS resemble those seen in eyes with primary congenital glaucoma. These findings include a wider uveal meshwork, a ciliary muscle that is directly attached to the trabecular meshwork, an under-developed scleral spur, and an iris root that is inserted anteriorly.
When glaucoma is present at birth, it is due to a malformation of the anterior chamber angle, and patients manifest typical signs of congenital glaucoma, including buphthalmos, anisometropia, and amblyopia. When it presents later, it is usually secondary to elevated episcleral venous pressure.4,49 When gonioscopy is performed in older children and adults with SWS and glaucoma, either minimal or no angle abnormality may be present. In addition, when gonioscopy is performed in older patients, blood is usually seen in the angle, correlating with an increase in episcleral venous pressure.
[51]
Another mechanism of glaucoma is thought to be premature aging of the trabecular meshwork that causes an early onset chronic open angle glaucoma, presenting in early adulthood. When neovascularization is present in the iris or angle, peripheral anterior synechiae may develop and result in secondary angle closure glaucoma.
[52]
Managing glaucoma in patients with SWS is complex because of early onset and resistance to conventional therapy. For early onset glaucoma with associated angle abnormalities, surgical intervention is usually required, with either goniotomy or trabeculotomy.
[46]
[49]
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. Olsen et al.
[53]
assessed the efficacy of goniotomy and trabeculotomy in 15 eyes. They found that the intraocular pressure (IOP) was controlled in 66.7% (10/15 eyes) after one or more goniotomy or trabeculotomy procedures, with a median follow-up of 5.4 years. The range of the patients’ age was from birth to 4 years, with a mean of 11.8 months. Iwach and colleagues reported the median stable interval of IOP control after a single goniotomy or trabeculotomy to be 8 and 21 months, respectively, in patients younger than 4 years.
[46]
In a study of 6 patients who underwent trabeculectomy and were followed from 9 months to 9 years, IOP was controlled in two eyes without medical therapy and in four eyes with medical therapy. Only one patient had a repeat trabeculectomy with adjunctive medical therapy to maintain adequate IOP.
[54]
A combined trabeculotomy with trabeculectomy was assessed in 10 eyes with glaucoma associated with SWS.
[55]
All eyes maintained IOP of less than 16 mm Hg without medication during a mean postoperative follow up of 27.8 months. Topical netarsudil can effectively lower intraocular pressure in patients with glaucoma and Sturge-Weber Syndrome, even when added as a 4th or 5th line agent.
[56]
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. Laser trabeculoplasty appears to be of limited use. If medical therapy is ineffective, trabeculectomy remains the procedure of choice for late onset cases, because it bypasses the episcleral venous system. Outcomes of trabeculectomy may be improved with the use of antimetabolites. Of note, trabeculectomy is associated with a much higher risk of choroidal effusions or suprachoroidal hemorrhages in eyes with SWS.
Glaucoma drainage devices have also been shown to be effective for glaucoma secondary to SWS. Hamush et al.
[57]
treated 11 eyes with the Ahmed glaucoma drainage device. The cumulative probability of success was 79% at 24 months, 59% at 42 months, and 30% at 60 months. Success was defined as an IOP < 21 mmHg on the last two measurements with no additional surgery or complications like hemorrhage or retinal detachments. A two-staged Baerveldt glaucoma drainage device was used in another study for the treatment of 10 eyes with SWS and glaucoma. Patients were, on average, 7 years old, and surgical success, defined as IOP<21 mm Hg after an average of 35 months of follow up, was 100%.
[58]
The two-stage technique allows encapsulation to occur around the plate for a few weeks prior to insertion of the tube into the anterior chamber, minimizing the risk of hypotomy and subsequent choroidal effusion or hemorrhage.
Another treatment option is cyclophotocoagulation (CPC) which can be performed 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.
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In a study of 16 children (16 eyes) with a mean follow-up of 8.87 years in which CPC was performed, 10 eyes (62.5%) maintained an IOP between 6-22 mm Hg without any complications associated with the treatment.
[60]
Klippel-Trenaunay-Weber Syndrome (KTS)
This syndrome, a rare cause of secondary glaucoma that should be distinguished from SWS, is characterized by a localized or diffuse capillary malformation that overlies a venous malformation and/or lymphatic malformation with associated soft tissue and bone hypertrophy.
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In addition to the extensive cutaneous hemangiomas affecting the face, similar to SWS, the trunk and limbs are involved. Dysplastic veins and hypertrophy of bone and soft tissues are often present in the affected extremity, a lower limb in 90% of the patients. Malformations of deep veins increase the risk of deep vein thrombosis and pulmonary embolism. Visceral organ involvement is associated with greater morbidity secondary to internal hemorrhage. Cerebral hemangiomas may also occur, causing epilepsy and mental retardation.
Prognosis
Patients with SWS have a lower life expectancy than does the general population.
[26]
When the leptomeningeal lesions are bilateral, patients usually have more severe neurological manifestations and a worse prognosis.
Summary
SWS is a rare, sporadic disorder with glaucoma being the most common ocular manifestation. Treatment of glaucoma requires an understanding of underlying pathology and mechanisms to guide appropriate surgical intervention. In general, lower surgical success and increased intraoperative and postoperative complications are observed in these patients when compared to other types of glaucomas. Several precautionary steps can be taken to minimize these complications, including preoperative reduction of IOP with hyperosmotic agents, placement of posterior sclerotomies prior to entering the eye, preplacement of flap sutures or additional and tight sutures during trabeculectomy, use of valved or two-stage glaucoma drainage devices, or radiotherapy of choroidal hemangiomas prior to intraocular surgery. Because multiple organs are involved in SWS, a multidisciplinary approach is recommended to deliver comprehensive care and optimize overall outcomes.
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