Capillary or venular malformation, also denoted as PWS or nevus flammeus, is the characteristic cutaneous manifestation in SWS.12 This lesion is already present at birth, of variable size, normally on one side though it may be bilateral, and of a color ranging from pale pink to purple. PWS can be confused with salmon patches (nevus simplex). Salmon patches are capillary malformations that present as a poorly delimited rose-colored macules, usually located in the central area of the forehead, philtrum, upper eyelids, vertex, and neck.13 The lateralized localization of PWS, its more intense color, and its well-defined borders help differentiate this lesion from salmon patches.

The risk of leptomeningeal or ocular involvement when facial capillary malformation (PWS) is present depends on the extent of the PSW and its site. Malformations that affect the frontal region have a higher risk than those that affect the lower part of the face.14 To date, studies have stratified risk assuming that facial PWS are distributed according to the areas of sensory innervation of the 3 trigeminal nerve branches: the frontal branch (V1), the maxillary branch (V2), and the mandibular branch (V3)15–18 (Figs. 2A-C). All studies agree that lesions with a highest risk of involvement are those affecting the V1 branch, the upper eyelid, or those that are bilateral and extensive (Fig. 3A and B). Thus, the incidence of leptomeningeal involvement or glaucoma in patients with capillary malformations with V1 involvement is between 8% and 15%, whereas if the involvement is bilateral or affects several dermatomes, the incidence is 28%.17 The risk that PWS with exclusively V2 or V3 involvement are associated with leptomeningeal involvement or glaucoma is almost negligible, according to most authors.17,18 However, in some studies, V2 involvement is considered to have a risk of 2%.17,18 This discrepancy may be because some authors have considered the lower eyelid as belonging to V2 whereas others consider that it belongs to V1.17,18

Figure 2.

Distribution of Port wine stain. A, Frontal branch (V1); B, Maxillary branch (V2); C, Mandibular branch (V3).

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Figure 3.

A, Port wine stain with extensive involvement; B, Port wine stain with bilateral involvement.

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This distribution of PWS according to the sensory trigeminal nerve branches has been widely debated. Waelchli et al.,13 after reviewing the distribution of facial PWS in 192 children, arrived at the conclusion that the lesions do not follow the sensory areas of the trigeminal nerve but rather follow 8 more or less repetitive areas of distribution. According to these authors, the area of the forehead between the midline of the forehead and a line that joins the outer canthus of the eye and the top of the ear, including the upper eyelids, is the only area with a risk of association. All patients with abnormalities in magnetic resonance imaging (MRI), seizures, or glaucoma, had involvement of this frontal area. Of note, though, is that this retrospective study only performed MRI on 4 patients with PWS outside this area. The frontal area mimics the distribution, in the area of the optic vesicle, of the frontonasal prominence and skin, which are derived from the frontal placode. The placodes develop their own vasculature, and so the authors postulate that facial PWS imitate the embryological vasculature and do not follow the sensory nerve distribution of the face. The frontal placode develops its vasculature from the prosencephalon and anterior mesencephalon, structures that will give rise to the brain and optical vesicle, thus explaining why the PWS in this area derived from the frontal placode are those with a risk of SWS.13,19

Facial PWS develop soft tissue hypertrophy in 60% of cases, bone hypertrophy in 13.8%, and formation of proliferative nodules or progressive ectasia in 43.8% (Fig. 4A and B). The mean age of onset of these changes is 9 years and the maxillary branch (V2) is the one which most frequently presents hypertrophy.20,21 Poor occlusion and greater dental exposition may result from excessive growth of the maxilla and jaw, leading to significant facial deformation22 (Fig. 5).

Figure 4.

A, Port wine stain with soft tissue hypertrophy; B, Port wine stain with formation of proliferative nodules.

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Figure 5.

Maxillary and mandibular growth.

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One of the manifestations of SWS is capillary-venous leptomeningeal malformation. Intracranial angiomatosis is usually ipsilateral to PWS, although it can be bilateral. It generally involves the occipital and occipitoparietal lobe and, at times, the entire hemisphere.1

Histologically, the cerebral vascular malformation consists of tortuous vascular structures and abnormalities in the thickened leptomeninges. Abnormalities are also observed in the deep draining veins, which are abnormally dilated. The underlying brain tissue may be atrophic and show neuronal loss, astrocytosis, cortical dysgenesis, and calcifications distributed perivascularly or in the cerebral cortex. It is thought that these are dystrophic calcifications caused by hypoxia. The leptomeningeal vessels of patients with SWS show overexpression of fibronectin and vascular endothelial growth factor (VEGF) as well as increased endothelial proliferation and apoptosis.4,23

The main clinical manifestations of leptomeningeal angiomatosis are seizures (75% to 90%), slowly progressive hemiparesis (25% to 60%), migraine-like vascular headaches (30% to 45%), delayed neuropsychological development (50% to 60%), episodes similar to cerebrovascular events, with acute transient hemiplegia, visual field defects, and behavioral problems.1,3 The seizures present in patients with SWS are the result of cortical irritation caused by cerebral vascular malformation through mechanisms of hypoxia, ischemia, and gliosis.24 Seizures are usually complex focal seizures or partial seizures with secondary generalization.23 Seizures first occur during the first year of life in 75% of patients and before the second birthday in 90%.25 Fever may trigger seizures in SWS. Patients without PWS but with leptomeningeal angiomatosis may present seizures during childhood or even as adults.14 When seizures first present before 2 years of age, they are more difficult to control and there is a greater risk of mental retardation.26,27 Progressive neurological deterioration in children with SWS is of ischemic origin, caused by altered cerebral perfusion and associated with elevated metabolic demand arising from prolonged seizure activity.4

Ocular vascular malformation consists of dilated tortuous venous vessels that may involve the conjunctiva, episclera, retina and/or choroid, leading to optical atrophy and blindness.23

Glaucoma is one of the most frequent ocular manifestations in SWS, affecting approximately 30% to 70% of patients.25,28,29 It is usually unilateral or ipsilateral to PWS, but this is not always the case.1 Glaucoma in SWS is thought to be caused either by increased episcleral venous pressure, a pathophysiological mechanism supported by the presence of blood within the Schlemm canal, or by abnormalities in the anterior chamber which interfere with normal outflow of the aqueous humor, resulting in increased outlet resistance.23,30 Glaucoma can be congenital or develop after birth. In 60% of the early forms, glaucoma is caused by abnormalities in the angle of the anterior chamber, whereas the cause of glaucoma in 40% of young people and young adults is elevated episcleral venous pressure.30

Choroidal hemangioma is present in 40% to 50% of patients with SWS, and can be circumscribed and/or diffuse. At times, the vascular choroidal lesion takes on a pathognomonic character, such as a reddish hue, which has been described as tomato catsup color.24 The choroid normally remains unchanged during childhood; however, in adolescents and adults, it may become notably thickened.30

Other ocular abnormalities have been reported, although less frequently, for example, heterochromia iridium, detached retina, strabismus, homonymous hemianopsia, phakomatosis pigmentovascularis, iris and choroidal neovascularization, and lens luxation.31,32

Patients with SWS may have hypothalamic-pituitary disorder, with growth hormone deficiency and central hypothyroidism.33–35

Although plain X-ray is not a technique of choice, it is possible to observe the classical gyriform cortical calcifications also known as railroad track appearance, which affect the intimal layer of the meningeal arteries. These are adjacent to the leptomeningeal angioma, mainly in the parietal and occipital region.26,36 Calcifications usually affect children aged 2 years, and so they are considered a late-onset finding.37

Brain tomography is a technique used frequently in the emergency room to assess children who present with hemiparesis or seizure. The characteristic findings are presence of reduced parenchymal volume, enlarged ventricle, and enlarged choroid plexus. From 1 year of age, computed tomography can detect calcifications (Fig. 6), which would not normally be visible in a plain X-ray. Computed tomography is also more sensitive for detecting calcifications than MRI.14,37

Figure 6.

Cranial computed tomography without contrast enhancement. Axial cut at the level of the lateral ventricles, showing multiple calcifications in both hemispheres with a curvilinear and gyriform pattern, associated with loss of brain volume at these sites.

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Brain MRI with gadolinium enhancement is the imaging technique of choice for diagnosis of SWS.28 With this technique, it is possible to visualize the leptomeningeal vascular malformation that confirms diagnosis of SWS (Fig. 7). Calcifications in MRI can also be detected in T2 sequences as images of cortical and juxtacortical hypointense signal. MRI can also detect abnormal venous drainage, reduced brain volume, enlarged ipsilateral choroid plexus, prominence of subependymal and medullary veins, loss of volume of the affected brain hemisphere, and accelerated myelinization underlying the leptomeningeal angioma.14,24,37 These changes are more evident after 1 year of age.38

Figure 7.

Cranial T1 magnetic resonance imaging, with gadolinium enhancement. Axial plane at the level of the mesencephalon, showing leptomeningeal thickening and uptake typical of leptomeningeal angiomatosis in a patient with SWS.

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The characteristic electroencephalogram (EEG) of patients with SWS is asymmetric, with decreased voltages and focal discharges in the affected brain hemisphere. EEG is also very useful for distinguishing migraines and seizure after cerebrovascular events as causes of the acute paroxysmal events.1

EEG in patients with SWS appears to change over time, becoming increasingly abnormal, with more frequent epileptiform activity.39

During the first years of life, the vascular malformation tends to be hyperperfused. The pattern changes to hypoperfusion at the end of the first year of life, even in patients without seizures,24,37 although these changes are accelerated by crises and progressive ischemia, hypoxia, and glucose deprivation in the parenchyma underlying the malformation, and these are responsible for the progressive neurological deterioration in patients with SWS.

Angiography is not routinely performed, but it can be useful in atypical cases to evaluate other associated vascular abnormalities (venous occlusion, thrombotic lesions, or arteriovenous malformations) or to identify large diploic vessels, thus avoiding bleeding in the event that craniotomy is necessary.24

The authors declare that no experiments were performed on humans or animals for this investigation.

The authors declare that they have followed their hospital's protocol on the publication of data concerning patients.

The authors declare that patient data do not appear in this article.