Abstract and Introduction
Background Facial port-wine stains (PWSs) are usually isolated findings; however, when associated with cerebral and ocular vascular malformations they form part of the classical triad of Sturge–Weber syndrome (SWS).
Objectives To evaluate the associations between the phenotype of facial PWS and the diagnosis of SWS in a cohort with a high rate of SWS.
Methods Records were reviewed of all 192 children with a facial PWS seen in 2011–13. Adverse outcome measures were clinical (seizures, abnormal neurodevelopment, glaucoma) and radiological [abnormal magnetic resonance imaging (MRI)], modelled by multivariate logistic regression.
Results The best predictor of adverse outcomes was a PWS involving any part of the forehead, delineated at its inferior border by a line joining the outer canthus of the eye to the top of the ear, and including the upper eyelid. This involves all three divisions of the trigeminal nerve, but corresponds well to the embryonic vascular development of the face. Bilateral distribution was not an independently significant phenotypic feature. Abnormal MRI was a better predictor of all clinical adverse outcome measures than PWS distribution; however, for practical reasons guidelines based on clinical phenotype are proposed.
Conclusions Facial PWS distribution appears to follow the embryonic vasculature of the face, rather than the trigeminal nerve. We propose that children with a PWS on any part of the 'forehead' should have an urgent ophthalmology review and a brain MRI. A prospective study has been established to test the validity of these guidelines.
The original description of Sturge–Weber syndrome (SWS) by William Sturge in 1879 was of a triad of extensive facial, scalp and truncal capillary malformation (port-wine stain, PWS), contralateral focal seizures suggested to be due to an ipsilateral abnormality on the surface of the brain, and ipsilateral intraocular vascular malformation with glaucoma. Kalischer confirmed the presence of an ipsilateral leptomeningeal vascular malformation on pathological examination in 1901, and in 1922 Weber described the radiological appearances of ipsilateral cerebral atrophy and the characteristic intravascular calcification in a patient with extensive bilateral facial, truncal and upper-limb PWS. Over the years the definition of SWS has expanded to include cases without cutaneous lesions, and variable distributions of brain and ophthalmological lesions.[5,6] Neurological features have been described in detail since the advent of computed tomography and magnetic resonance imaging (MRI), revealing angiomatosis (a capillary–venous malformation)[7,8] of the leptomeninges, atrophy and calcification of the affected cerebral hemisphere, absence of superficial cortical veins and/or dilated deep-draining veins, and vascular malformations involving the choroid plexus.[5,9–11] Recent advances in functional imaging have demonstrated decreased cerebral perfusion and network connectivity in affected areas.[12–14] Clinical neurological problems include seizures (often but not always contralateral focal motor seizures), neurodevelopmental delay, headache and stroke-like episodes. The ophthalmological features in SWS are enlarged venous vessels affecting the conjunctiva, episclera, retina and/or choroids, associated with glaucoma, retinal detachment and choroidal haemorrhage.[1,16,17]
Therapeutic studies have shown that early diagnosis and treatment of SWS may reduce ensuing complications, based on a new understanding of the pathogenesis of disease progression. The typical MRI findings of atrophy and calcification are now considered to be the consequence of chronic cortical hypoxaemia due to vascular stasis and decreased perfusion in the cortex underlying the leptomeningeal angioma.[6,14] Imaging studies during the characteristic stroke-like episodes have suggested decreased perfusion of affected areas.[18,19,20] This new understanding has led to the administration of prophylactic aspirin,[21,22] and although randomized controlled trials are lacking, current data show reduced occurrence of stroke-like episodes and seizures. The potential benefits of diagnostic MRI and use of prophylactic aspirin need to be considered in relation to the potential adverse effects in the individual patient by the clinician. Given the severity of seizures and the association with acute neurological deficit, there is a rationale for the diagnosis of brain involvement in asymptomatic infants and children. Furthermore, as seizure activity correlates with poorer cognitive prognosis,[23,24] some authors recommend prophylactic antiepileptic treatments. Early treatment of glaucoma is known to be critical in preserving visual function, and prompt diagnosis in SWS is important as glaucoma can be present from birth. Early identification of patients with facial PWS who may be at risk of SWS is therefore crucial in instigating early clinical and radiological investigation, and, where appropriate, prophylactic therapy.
Facial PWSs are a far more common occurrence than SWS, with an incidence of approximately 1 in 300[26,27,28] for the former and an estimated incidence of between 1 in 20 000 and 1 in 50 000 for the latter.
In infants true PWS should not be confused with a salmon patch (naevus simplex). Naevus simplex is a transitory functional capillary lesion occurring in about 40% of newborns, which presents most commonly as an irregularly bordered, symmetrical pink macule overlying the midline of the neck, the forehead or the upper eyelids.
SWS occurs sporadically with equal frequency in boys and girls. Early studies of the relationship between facial PWS phenotype and risk of SWS implicated PWS in the ophthalmic (V1) division of the trigeminal nerve, a bilateral distribution, and lesions affecting the upper eyelids.[29,30] However, more recent studies comparing PWS phenotype with cerebral and ocular phenotype have shown that while bilaterality and V1 distribution appear to be a risk factor, more extensive PWS with additional V2 and/or V3 involvement of the trigeminal nerve contribute to the risk of SWS.[31,32]
The aim of this study was to correlate facial PWS phenotype with intracranial and intraocular abnormalities, to review the validity of the trigeminal nerve classification, and to propose guidelines for investigation of facial PWS that can be used in our population for future prospective studies.
The British Journal of Dermatology. 2014;171(4):861-867. © 2014 Blackwell Publishing