Synonyms: fourth phacomatosis ('mother-spot') or encephalotrigeminal angiomatosis
Sturge-Weber syndrome (SWS) is a neurocutaneous disorder classically presenting with:
- A facial port-wine stain affecting the facial skin (in the distribution of some or all divisions of the trigeminal nerve).
- Vascular eye abnormalities.
- An ipsilateral occipital leptomeningeal angioma.
- The leptomeningeal malformations lead to venous hypertension and subsquent hypoperfusion of the underlying cortex.
Children with SWS often develop progressive problems including glaucoma, seizures, stroke, and intellectual disability. A genetic mutation disrupting vascular development causes both the Sturge-Weber syndrome and port-wine stains.[2, 3]The severity and extent of presentation are thought to be determined by the developmental time point at which the mutation occurred.
- SWS is a phacomatosis, ie one of a group of congenital and hereditary diseases characterised by the development of hamartomas in various tissues. Other examples include tuberous sclerosis and neurofibromatosis. SWS cases appear randomly without clear evidence of familial inheritance.
- It results from an early embryologic malformation of vascular development.
- This is driven by a genetic mutation which increases cell proliferation and inhibits apoptosis.This mutation was identified and described in May 2013.
- Neurological deterioration is thought to be secondary to impaired blood flow to the brain and is worsened by the presence of seizures.
- Normally (ie where there is no SWS) a vascular plexus develops around the cephalic portion of the neural tube, under the area of ectoderm which is destined to become facial skin.
- This plexus develops in the sixth week and regresses around the ninth week of gestation.
- Residual vascular tissue in SWS forms the angiomata of the leptomeninges, face, and ipsilateral eye and also has secondary effects on surrounding brain tissue, including:
- Ischaemia (caused by 'vascular steal phenomenon').
- Venous occlusion, thrombosis and infarction.
- Recurrent seizures, status epilepticus, intractable seizures, and recurrent vascular events may aggravate cortical ischaemia.
- This leads to more calcification, gliosis, and atrophy, which in turn increase the chance of seizures and neurological deterioration.
The cutaneous angioma is called a port-wine stain. These are usually seen in the ophthalmic and maxillary distributions of the trigeminal nerve, although it is now realised that development follows the embryological pattern of facial development, rather than the neurodevelopmental pattern.
SWS is referred to as complete when both central nervous system and facial angiomas are present, and incomplete when only one area is affected. The Roach Scale has been traditionally used for classification, although a proposed prognostic system of classification suggests that the best predictor of adverse outcomes is a port wine stain involving the 'forehead area', stretching from the midline of the forehead to 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, and corresponds well to the embryonic vascular development of the face.
Abnormal MRI is a better predictor of all clinical adverse outcome measures than port-wine stain distribution:
- Both facial and leptomeningeal angiomas.
- May have glaucoma.
- Facial angioma alone.
- May have glaucoma.
- Isolated leptomeningeal angioma.
- Usually no glaucoma.
- Incidence is 1/50,000 live births.
- Males and females are equally affected.
- There is no racial predilection.
Not all infants with facial naevi have SWS. Incidence of SWS has been reported to be 8-33% in those with a port-wine stain.
- Port-wine stains affecting the entire V1 distribution predict strongly for underlying neurological and/or ocular disorders that require ongoing ophthalmological surveillance and/or neurological management.
- Although classical SWS encompasses a triad of clinical manifestations, incomplete forms are not uncommon.
- SWS is believed to be a result of vascular malformations of associated structures derived from the neuroectoderm (facial skin, eye, and parieto-occipital region of the brain and leptomeninges) during the first trimester.
- SWS always involves the upper face and eyelid, although it may also appear on the lower face, trunk and oropharyngeal mucosa.
- More than two thirds of patients with SWS present with a unilateral capillary malformation; approximately 25% exhibit the port-wine birthmark in the sensory territories of all three trigeminal branches of both sides.
- Macular lesions can be progressive.
- The ipsilateral eye to the naevus commonly shows buphthalmos and glaucoma.
- There may be macrocephaly and choroidal haemangiomata.
- Focal tonic-clonic seizures typically appear in the first year on the opposite side to the naevus.
- The incidence of epilepsy in patients with SWS is 75-90%, and around 75% of these will appear in the first year of life.
- The seizures may become generalised and evolve into other types, such as drop attacks, myoclonic or infantile spasms.
- The seizures are often very frequent, and prolonged seizures may occur.
- In many cases seizures are associated with slowly progressive hemiparesis.
- The incidence is approximately 33%.
- The severity of weakness is closely related to the severity of the seizures.
- As the child grows the weakness may become more severe and permanent.
- The seizures may be resistant to drug treatment.
- Developmental delay and general learning disability are related to the degree of neurological involvement. These conditions occur in 50-60% of patients and are more likely in patients with bilateral involvement.[1, 3, 5]
- Headaches occur secondary to vascular disease. The symptoms are similar to a migraine headache.
- The diagnosis of SWS is suspected when a newborn has a facial port-wine birthmark.
- Diagnosis of SWS is made if the cutaneous port-wine stain is associated with either brain or eye involvement.
- This risk is about 25% when the skin port-wine birthmark involves most of the ophthalmic distribution of the trigeminal nerve on the face.
- The risk increases to 33-50% with bilateral or more extensive facial port-wines stains.
- Some patients do not have facial port-wine stain but are diagnosed on the basis of clinical findings and leptomeningeal angiomata alone.
- The maximum extent of disease may require a combination of structural and functional imaging, as some investigations may demonstrate abnormalities not detected by others. Information about the vasculature as well as lesion depth is possible with use of photoacoustic imaging (PAI).
- The diagnostic algorithm should start with ultrasound, followed by non-invasive MRI or CT, and finally invasive investigations like angiographies when indicated.
- Expected lesions include the vascular malformation, with capillary and/or venous malformation involving the face, choroid of the eye, and leptomeninges.
- Chronic cerebral ischaemia may lead to parenchymal atrophy, and enlargement of the medullary and subependymal veins, enlargement of the choroid plexus on the same side, and cortical calcification.
- Cortical calcifications resulting from leptomeningeal vascular malformations situated along the space between the pia mater and the arachnoid membrane often lead to a classical CT appearance of 'tram-track calcifications.[6, 7]
- Imaging may also demonstrate underlying atrophy of the cerebral hemisphere.
- MRI is now the main imaging modality used in the primary assessment of the nature and extent of the disease.
- Cross sectional images may now be combined to produce 3D imaging of the Structures and abnormalities involved.
- CT scanning is more sensitive in the detection subcortical calcifications, but MRI is more sensitive in the demonstration of the extent of other brain abnormalities.
- Enlarged deep medullary and subependymal veins can be identified at contrast material–enhanced MR imaging. These are probably a result of slow flow or thrombosis in the superficial venous system and the subsequent shunting of blood through deep medullary veins.
- Orbital associated malformations are particularly well defined by contrast-enhanced orbital MRI. Ocular lesions include those caused by buphthalmos, as well as scleral or choroidal angiomas, choroidal detachment and subacute hemorrhage in the globe.
- Choroid plexus enlargement may be seen in the ipsilateral lateral ventricle.
MRA (magnetic resonance angiogram)
- This uses MRI to generate images of the blood vessels in SWS.
- Flow-dependent MRA may produce functional images of the vasculature, whilst contrast enhanced techniques are flow independent.
- Amongst techniques in development is 4D Dynamic MR Angiography (4D-MRA): which will allow imaging of the vascular tree with division of arterial and venous phases and visualisation of their dynamics.
Transcranial Doppler ultrasound
- This noninvasive technique is useful in early assessment of the vascular malformation.
- High resistance patterns that are typical of venous stasis (and which may contribute to chronic hypoperfusion of brain tissue have been picked up by this method).
- Ultrasound is limited in its detection of deeper abnormalities and is highly operator-dependent so that findings should be correlated with those on MRI.
- This may show calcifications in infants and even in neonates.
- The characteristic sign is of 'tram-track calcifications', a set of serpentine parallel opacities, although these are not always initially present.
- Calcification can be more extensive, however, with frontal lobe and/or bilateral involvement.
- Other findings include brain atrophy, again with calcifications, ipsilateral choroid plexus enlargement, abnormal draining veins, and a breakdown of the blood-brain barrier with seizures.
- This is used for evaluation of seizures and for localisation of seizure activity in refractory seizures when epilepsy surgery is considered.
- Typical findings include reduced background activity, polymorphic delta activity and epileptiform features.
- This technique uses radio-tracers to image the lymphatic system.
- It is more commonly used for sentinel node mapping when staging the axilla in early breast cancer. It may be used for determining the extend and involvement of the lymphatic system in SWS.
- Differentiation of vascular from lymphatic malformation can otherwise be difficult.
- X-ray has been largely superseded in SWS due to the availability of newer imaging techniques give more useful and detailed Information.
- X-ray, when used, may show the tram-track sign of intracranial calcification in the occipitoparietal region.
- Secondary skull changes include a thickened diploic space with ipsilateral frontal sinus enlargement, together with enlargement of mastoid cells with elevated petrous ridges.
Cosmetic camouflage creams can be used to help to conceal the port-wine stain. It is more effective than over-the-counter foundation/make-up because it is both lightweight and available in a wide range of colours.
Carbamazepine is an anticonvulsant effective for treatment of complex partial seizures:
- The major mechanism of action is reduction of sustained high-frequency repetitive neural firing.
- The chance of achieving seizure control with medical therapy in SWS varies. There is a wide range of reported seizure control in studies, with no overall consensus.
- The age of seizure onset may be a prognostic sign for ultimate seizure control. Early onset is associated with refractory seizures and developmental delay.
- Pulsed dye laser (PDL) treatment is used for port-wine stain:
- This laser treatment is particularly effective in improving facial port-wine stains in infants ≤6 months of age.
- This is often recommended for lesions near the eyes or orifices, or if the lesions bleed, ulcerate or become infected.
- Significant re-darkening of port-wine stains has been noted at 10-year follow-up.
- External laser treatment of vascular abnormalities may not be effective if they are deep, because the laser beam does not penetrate far beneath the skin.
- Intralesional photocoagulation is a laser treatment that involves inserting a laser fibre into the lesion to deliver the light deep within it.
- Combined use of PDL therapy and topical imiquimod may produce superior results to PDL alone.
- Surgical options are available for focal seizures refractory to medical treatment:
- Surgical procedures include focal cortical resection, hemispherectomy, corpus callosotomy and, recently, vagal nerve stimulation (VNS).
- Criteria for medical intractability should be fulfilled before considering surgery.
Although, apparently neurologically normal in the first year of life, over half of cases are found to have severe learning disability in later childhood. This is in part due to prolonged generalised seizures and use of anticonvulsants, but abnormalities of vascular supply and 'vascular steal syndromes' may also play a signficant role in producing a degree of cortical atrphy.
Although it is possible for the birthmark, and the associated atrophy in the cerebral cortex, to be present without symptoms, most infants develop convulsive seizures during their first year of life. There is a greater likelihood of intellectual impairment when seizures start before the age of 2 and are resistant to treatment.
As might be expected, studies have found that cortical volume analysis (representing cortical atrophy) on MRI correlates well with impairment and prognosis.
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