Sturge-Weber syndrome (SWS) is a neurocutaneous syndrome characterized by angiomas involving the face, choroid, and leptomeninges. The facial capillary vascular malformation is also known as "port wine stain" or "nevus flammeus" and usually is seen in the territory of the trigeminal nerve. Sturge-Weber syndrome is also called encephalotrigeminal angiomatosis. It is the third most common neurocutaneous syndrome after neurofibromatosis and tuberous sclerosis .
Sturge-Weber syndrome is a sporadic developmental disorder caused by somatic mosaic mutations in the GNAQ gene which is located on the long arm of chromosome 9. It has been postulated that the presence of facial and pial angiomas suggest the persistence of primordial sinusoidal vascular channels. Another possibility is that the superficial venous drainage of the brain never fully develops and the capillaries and small venous channels become dilated to compensate.
The incidence of Sturge-Weber syndrome is not well known and estimated to be 1 in 20,000-50,000 live births.
Facial nevus is composed of multiple thin-walled vessels that resemble capillaries. The neuropathological finding is an angioma which consists of multiple capillaries and small venous channels and usually confined to the pia mater. There is a relative lack of superficial cortical veins, and the blood is shunted to the deep venous system by the enlarged medullary veins which result in stasis and ischemic changes.
A seizure is usually the first neurological manifestation of Sturge-Weber syndrome. Infantile spasms are seen in approximately 90% of affected patients in the first year of life followed by atonic, tonic, or myoclonic seizures. Increasing hemiparesis commonly accompanies seizures. Seizures progressively become refractory to medication . Facial nevus (port wine stain) is another common finding and typically seen along the ophthalmic or maxillary segment of the trigeminal nerve (forehead, cheeks). It is typically unilateral, present at birth, and does not change with the age of the patient . This appearance is in sharp contrast to the infantile hemangioma which is more common than port-wine stain; however, it is not present at birth. It slowly grows and is followed by involution. A child with a facial port wine stain has 10% to 35% risk of brain involvement. If there is involvement of both upper and lower eyelids, then the risk of glaucoma increases up to 50%. Glaucoma is almost always ipsilateral to the facial port-wine stain. Not all patients with port-wine stains have Sturge-Weber syndrome. Patients with Sturge-Weber syndrome may present with cerebral symptoms without facial findings. Ocular involvement in infancy may present with increased vascularity of the conjunctiva, eye enlargement, strabismus, and increased tearing. Other symptoms are mental retardation, early handedness, and gaze preferences. Diffuse choroidal hemangioma is seen in about 20% of patients with Sturge-Weber syndrome and is usually on the same side as a facial port-wine stain . Choroidal hemangiomas grow slowly and usually do not cause any symptoms. Retina overlying the choroidal hemangioma may be normal; however, it may also show pathological changes such as epithelial atrophy/proliferation, drusen formation or detachment.
Diagnosis of Sturge-Weber syndrome is based on typical clinical symptoms, facial appearance, and brain MRI findings. The ophthalmic examination is required to rule out glaucoma. Ocular ultrasound can demonstrate diffuse choroidal thickening which suggests choroidal hemangioma. Gyriform calcifications can be seen on the skull radiographs and classically described as "tram-track sign." CT is the best modality to detect calcifications and also show the other changes such as cortical atrophy and leptomeningeal enhancement on the post-contrast studies. However, CT uses ionizing radiation, and the routine use of CT in children is not recommended. Therefore, MRI of the brain with contrast is the recommended imaging modality of choice. The most common locations are occipital and posterior parietal/temporal lobes. The MRI findings depend on the stage of the disease. In the early phase, there is transient hyperperfusion with accelerated myelin maturation, leptomeningeal enhancement (seen as serpiginous enhancement along the sulci) and restricted diffusion if there is associated acute ischemic event. In the late phase, the increased T2 signal is seen in the region of gliosis with decreased pial enhancement and cortical atrophy. There is a lack of superficial cortical veins with prominent deep medullary/subependymal veins and enlarged choroid plexus. Gyriform calcifications are best seen on T2* or SWI (susceptibility weighted images) and appear as areas of signal loss along the gyri in a serpentine pattern. Patient with cutaneous and ocular manifestations with normal brain MRI at one year of age are unlikely to have brain involvement in the future. Choroidal angiomas can be seen on MRI as increased enhancement along the posterior choroid layer of the globe. FDG-PET may be a useful modality to study the cerebral metabolism in patients with Sturge-Weber syndrome. The affected area is usually hypermetabolic in the early stages with hypometabolism in the late stage . PET may be useful in surgical planning when cortical resection is required for the treatment of intractable seizures.
There is no specific treatment for Sturge-Weber syndrome. The primary aim is to minimize seizures activity with anticonvulsive medications. Surgery may be considered in patients who fail the medical management and continue to have refractory seizures. The surgical procedures for Sturge-Weber syndrome include hemispherectomy or focal resection of the seizure focus. Patients with bilateral involvement are typically not good candidates for surgery . Low-dose aspirin has also been shown to be effective in decreasing the frequency of seizures and stroke-like episodes . An annual ophthalmologic examination is recommended even if the early evaluation does not detect glaucoma. The goal of glaucoma treatment is to reduce the intraocular fluid which decreases the intraocular pressure with subsequently decreased the risk of vision loss. The topical medication is considered first for late-onset glaucoma. The surgery is considered for patients with early-onset glaucoma and associated angle abnormalities and includes goniotomy or trabeculotomy. Further surgeries such as trabeculectomy or glaucoma drainage device may be considered for resistant patients . The port-wine stain can be treated with laser photocoagulation which results in irreversible damage to the blood vessels without damage to the other skin components.
Differential diagnoses of Sturge-Weber syndrome are Klippel-Trenaunay-Weber syndrome, blue rubber bleb nevus syndrome, Wyburg-Mason syndrome, and PHACES (posterior fossa abnormalities, hemangiomas, arterial anomalies, cardiac, eye, and sternal anomalies). However, the Sturge-Weber syndrome can easily be differentiated from these conditions based on clinical history, physical examination, and brain MRI findings.
The management of Sturge-Weber syndrome is multidisciplinary with the involvement of a geneticist, pediatricians, pediatric ophthalmologists, pediatric radiologists, pediatric neurologists, nurse practitioner, and pediatric neurosurgeons. There is no cure for the syndrome and all treatments are symptom-based. Besides preventing seizures, the children need an ophthalmology follow up because of glaucoma. The skin lesions are managed by the dermatologist. The prognosis for these patients is guarded and depends on the severity of associated anomalies. (Level V)
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