Pediatrics

Sturge Weber

OVERVIEW: What every practitioner needs to know

Are you sure your patient has Sturge-Weber syndrome? What are the typical findings for this disease?

Sturge-Weber Syndrome (SWS), also called encephalofacial angiomatosis, is a congenital neurocutaneous disorder characterized by:

  1. A 'port-wine stain', or cutaneous nevus flammeus, involving the upper face or forehead. The port-wine stain is usually unilateral, but can sometimes be bilateral.

  2. Leptomeningeal angiomatosis (capillary-venous malformation of the pia and arachnoid matter)

  3. Vascular anomalies of the eye

The most common problems seen in patients with SWS include (with approximate incidence):

  1. Focal motor or complex partial seizures (75%-90%; generalized seizures can also occur)

  2. Glaucoma (up to 70%; as well as vascular eye findings such as hemangioma of the choroid)

  3. Hemiparesis and visual field deficits (50%)

  4. Stroke-like episodes (acute onset of new functional deficits, which may recover slowly and not return to the previous baseline functioning)

  5. Headaches (60%)

  6. Cognitive, behavioral, and psychiatric problems (incidence varies by specific feature)

What other disease/condition shares some of these symptoms?

Port-wine stains are blanching lesions representing deoxygenated blood present in underlying dilated veins. Port-wine stains are among the most commonly occurring vascular malformations (about 3 in 1000 people), and most children with port-wine stains do not have SWS. Only children with port-wine stains which are present in the approximate locations of the V1 and V2 dermatomal regions of the trigeminal nerve are at risk for SWS. The risk is increased if the port-wine stain affects the upper or lower eyelid.

There are no other clinical syndromes which present with the combination of a facial port-wine stain and leptomeningeal angiomatosis. Extremely rarely, SWS (defined by the presence of leptomeningeal angiomatosis) and resultant complications can occur in the absence of a port-wine stain.

Port-wine stains in V1 or V2 body locations can be associated with other syndromes, such as Klippel-Trenaunay syndrome or Parkes Weber syndrome. However, these disorders do not typically involve the central nervous system.

Certain intracranial vascular lesions, such as arteriovenous malformations or cavernomas, can result in similar symptoms as SWS, but are not associated with port-wine stains and would not be considered SWS unless there was also leptomeningeal angiomatosis.

What caused this disease to develop at this time?

SWS is a sporadically occurring disease occurring in roughly 1 in 50,000 people. There are no known predisposing factors, apart from the presence of any associated facial port-wine stain. SWS is not inheritable, and there are currently no known environmental risk factors.

Although the port-wine stain is always present at birth, the abnormalities seen in SWS may not appear until much later. Focal seizures are usually the earliest symptoms, which can begin in infancy. Other features that may present in infancy are any symptoms typical of unilateral brain dysfunction, for example early handedness, hemiparesis and gaze preference.

Seizures may not present until childhood or even adulthood, but epilepsy is diagnosed at some point in up to 75% of people with SWS and unilateral port-wine stains, and in 90% of those with bilateral port-wine stains.

The rare cases of SWS in which there is not a port-wine stain tend to present later in life, with less severe complications and better outcomes. These cases are only discovered when there are neurological symptoms severe enough to lead to brain imaging and lead to the discovery of leptomeningeal angiomatosis.

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

Diagnosis of SWS is based on clinical and radiological findings. At present, there are no laboratory tests to aid in the diagnosis.

Would imaging studies be helpful? If so, which ones?

The diagnosis of SWS requires radiologic confirmation of leptomeningeal angiomatosis, which is best observed with magnetic resonance imaging of the brain with gadolinium contrast. Leptomeningeal angiomatosis is usually present over the occipital area. However, leptomeningeal angiomatosis can occur in any region of the brain ipsilateral to the port-wine stain.

Leptomeningeal angiomatosis appears on T1-weighted post-contrast magnetic resonance (MR) imaging as enhancement of the meninges. Depending on the duration and severity of the symptoms, there will also be atrophy of the ipsilateral brain. White matter changes (both hyperintense and hypointense lesions) can also be seen, likely related to ischemia. The choroid plexus is often enlarged.

Calcifications are typically seen in the area of the leptomeningeal angiomatosis, particularly as the disease progresses, and will likely not be present early on. The calcifications are best seen with computed tomography (CT); however, they can also be seen with gradient recalled-echo sequences in MR imaging.

Conventional angiography involving intra-arterial radio-opaque contrast injection is no longer necessary to diagnose SWS. Angiography has demonstrated slow venous flow in the areas of angiomatosis. Superficial cortical veins are sparse, and deep venous structures, which drain into the larger central veins, are often engorged and tortuous consistent with increased venous pressure. Arterial flow is generally normal.

Note that early in the disease, such as in infancy, imaging may be normal, because the brain findings in SWS evolve and typically worsen over time. Thus, follow-up imaging is important in any patient with certain facial port-wine stains (as discussed below).

Confirming the diagnosis

SWS can be confirmed in any patient with a facial port-wine stain and neurologic symptoms when an MRI of the brain with contrast reveals leptomeningeal angiomatosis.

However, there are no standardized testing guidelines for asymptomatic children who present with port-wine stains. The risk of clinically relevant neurologic or ocular findings with any facial port-wine stain is approximately 8%-10% (see Ch'ng and Tan, 2008). This risk is estimated to increase to approximately 75% if the port-wine stain involves the entire V1 distribution.

Typically, an MRI of the brain with contrast should be performed in any child with a port-wine stain of the upper face. Given that imaging can be negative early in SWS, many experts recommend an additional screening MRI between 1-2 years of age if no symptoms of SWS become evident. However, there are no studies available which have compared outcomes based on detecting SWS syndrome prior to the development of neurologic symptoms versus waiting until there are clinical findings apart from the port-wine stain.

All children with port-wine stains of the upper face, and particularly if the eyelid is involved, should be referred to an ophthalmologist to check for elevations in intraocular pressure (i.e., glaucoma) and ocular vascular lesions. There are no established guidelines for the frequency of screening eye exams in patients with port-wine stains but without evidence of neurologic complications on exam or on imaging. Infants with confirmed SWS are at high risk for ocular complications and should be seen frequently by an ophthalmologist.

Children who do not have port-wine stains in the V1 areas of the face are not at risk for developing SWS. However, it is reasonable to screen for neurologic and ocular disease in a child with a port-wine stain involving the lower eyelid, given that this area is variably associated with either V1 or V2.

If you are able to confirm that the patient has Sturge-Weber syndrome, what treatment should be initiated?

  • At present, there is no known treatment which is successful at directly treating the primary cause of SWS, which is the abnormal vasculature and associated leptomeningeal angiomatosis. Thus, the treatment of SWS is primarily aimed at treating each of its varied manifestations individually.

    Seizures:

    Children with asymptomatic SWS, or a child with a highly suspicious port-wine stain, are at high risk for developing seizures and epilepsy. As outlined by Anne Comi (2011), caregivers and medical providers of these children should be counseled about the signs and symptoms of seizures, particularly focal motor seizures, and a treatment plan with the patients' physicians should be in place to quickly and aggressively treat and prevent seizures. Rectal diazepam should be considered for home use should a seizure be noted.

    Because the majority of patients with SWS will have more than one seizure, a long-term antiepileptic drug should be started after the first seizure. Drugs such as carbamazepine or oxcarbazepine, which are used in focal seizure disorders, should be the first-line treatment. Other anti-epileptic medications which can be considered include valproate, topiramate, levetiracetam, and phenobarbital. Because seizures in SWS can cluster, it can often be difficult to determine if a particular medication has been efficacious.

    Seizures in SWS can be precipitated by illness and fever; therefore, basic prophylaxis such as routine vaccinations and yearly flu-shots are advised.

    As with any patient with medically refractory seizures, resective brain surgery should be a consideration when seizures are frequent despite aggressive pharmacologic management. This is particularly true in SWS, where the seizures themselves may contribute to worse outcomes. A majority of patients who undergo hemispherectomy can become seizure-free (Kossoff et al. 2002); however, there can be significant morbidity after surgery. The indication and timing for surgery is not agreed upon. There is conflicting evidence regarding whether early surgery will lead to improved physical and developmental outcomes (see Bourgeois et al. 2007 vs Carson et al. 1996). Any child who may be a surgical candidate should be referred to a pediatric epilepsy center.

    Antiplatelet therapy:

    Aspirin has been used in the treatment of SWS, because one of several mechanisms of injury postulated for SWS is that venous stasis results in microthrombi and possibly worsened ischemia. Low-dose aspirin (3-5 mg/kg/day) is considered safe, and seems to reduce the number of seizure episodes (Bay et al. 2011), although controlled studies are lacking. In addition, there are no data to aid in the decision of whether to begin aspirin therapy in SWS prior to the onset of neurologic symptoms.

    Eye disease:

    The incidence of glaucoma in SWS is between 30%-70%, and is always on the involved side in unilateral disease. In patients with bilateral port-wine stains, glaucoma can be either unilateral or bilateral. There is a bimodal distribution, with approximately 60% developing glaucoma early in childhood. The remaining cases do not typically develop until later in childhood or adulthood. Early onset glaucoma can result in buphthalmos (an enlarged eyeball), while late-onset glaucoma does not. According to Khaier et al. (2011), either the presence of port-wine stains on both upper and lower lid or the presence of episcleral hemangioma are independent risk factors for the development of glaucoma. These children should have frequent screening and follow-up with ophthalmology, initially as often as every 3-6 months.

    Glaucoma should be treated initially with topical pharmacologic agents. Trabeculectomy is reserved for patients who fail treatment with eye drops. However, due to the increased episcleral pressure seen in SWS, there is increased risk of complications.

    Headaches:

    Almost 50% of patients with SWS will have headaches, particularly migraine headaches. There is no firm evidence to suggest that headaches in SWS should be treated differently than in any other child without SWS. However, there is anecdotal evidence that headaches may precede seizure events or stroke-like episodes in SWS; thus, headaches warrant particularly aggressive treatment and prevention.

    Conventional treatments for headache symptoms, such as ibuprofen at the first sign of headache, may suffice in many patients, but when not effective, an abortive treatment with a triptan is often necessary (see Lewis, 2010 for a review). However, headaches are usually frequent enough that prophylactic medications are needed. There are many classes of medications which have been shown to be useful for headache prevention. However, in any child who has both headaches and seizures, it would be reasonable to tend toward those which are also anti-epileptics, such as topiramate and valproic acid.

    Behavioral, Cognitive and Psychiatric Problems:

    Although definitive studies on the incidence of developmental and psychiatric complications in SWS are lacking, many patients with SWS suffer from all manner of cognitive, mood, and behavioral issues. Children with SWS can exhibit speech and language delays, sleep disturbances, anxiety, mood problems, hyperactivity , and inattention, etc. (For a recent study and discussion, see Turin et al. 2010). Children with SWS should have developmental assessments and neuropsychological testing to assess for problems, and screening and treatment for mood symptoms with referral to psychiatry if necessary.

    Port-wine stain:

    Port-wine stains are not directly responsible for any symptoms seen in SWS. Lesions will not grow larger in extent with age; however, they can thicken, elevate, and appear roughened over time. Laser therapy with flashlamp-pumped pulsed dye laser is frequently performed in order to diminish the discoloration and reduce the social complications of having a prominent facial lesion. Many children will begin treatment during infancy. There is a relatively new hypothesis of the pathophysiology of SWS which attributes the SWS to a simple lack of cortical bridging veins and elevated venous pressure. Thus, the port-wine stain forms as a network of collateral veins (Parsa, 2008). One implication of this hypothesis would be that treatment of the port-wine stain could reduce collateral blood flow, and exacerbate glaucoma or even intracranial disease. The only study which has attempted to address this concern did not find an association with laser therapy and worsened ocular disease (Quan et al. 2010); however, additional studies are needed.

    Trauma:

    There are case studies which suggest that hemiplegia can be transiently worsened after minor head trauma in children. Thus, reasonable precautions should be taken to avoid situations where trauma may occur, as in certain sports.

    Support:

    Patients and families can be put in contact with the Sturge-Weber Foundation (www.sturge-weber.org) for resources and support.

What are the adverse effects associated with each treatment option?

In general, the adverse affects of the treatments for the various manifestations are ones that are typical of the drug used in the general population for the treatment of that particular condition. Two possible exceptions may be the increased risk of complications in glaucoma surgery, given the elevated venous pressure and the hypothesized theoretical risk of worsening disease with treating port-wine stains with laser therapy.

What are the possible outcomes of Sturge-Weber syndrome?

The long-term clinical outcome and prognosis seen in SWS is highly variable. Any of the more common symptoms (seizures and status epilepticus, hemiparesis, cognitive delays, headaches, and stroke-like episodes) may manifest in infancy, or not until adulthood. Long periods of stable disease may be followed by sudden worsening.

To a first approximation, patients with more extensive involvement of the brain or with bilateral disease and a larger area of leptomeningeal angiomatosis will have worse outcomes. However, some patients with SWS will have minimal symptoms, while others can have debilitating seizures and motor findings despite minimal intracranial disease. Counseling a patient and family can thus be very difficult. There is some evidence that a poor prognostic factor is early seizure onset, such as onset in infancy. However, the data are unclear, and heavily disputed.

In general, though, patients with higher seizure frequency will have less favorable outcomes, while those who do not have recurrent seizures have a much better overall prognosis.

What causes this disease and how frequent is it?

SWS is a sporadic disorder affecting boys and girls equally and occurring in roughly 1 in 50,000 births. The cause of SWS is not currently known. However there are some theories based on the anatomic and functional observations in SWS.

During the first trimester of embryologic development, there is a primitive venous plexus that matures to form the veins of the face, scalp, meninges, and brain. The tissue which will form the skin of the upper face is thought to initially be near the tissues which will form posterio-lateral areas of the brain. Maldevelopment of the venous plexus in this area is thought to explain the association between the facial port-wine stains and the (most commonly) parieto-occipital location of the leptomeningeal angiomatosis. This maldevelopment results in a decreased number of cortical bridging veins and other features of abnormal vasculature in SWS, which in turn is thought to result in decreased outflow of venous blood and elevations in venous pressure.

Increased venous pressure, along with possibly other abnormalities of the actual vessels, may lead to several possible mechanisms of injury such as microthrombosis and obstructive ischemia or ischemia due to stasis, and altered permeability of the vasculature and blood-brain barrier.

Another theory that has been promoted recently is that all pathology seen in SWS can be explained merely by local primary venous dysplasia in the meninges (Parsa, 2008). This results in venous hypertension and leads to engorgement of communicating venous networks and blood flow through alternative venous pathways. Flow patterns in the brain and cavernous sinus can be reversed, and pressure is transmitted via the ophthalmic veins to facial veins of the upper face, causing the port-wine stain and also accounting for ocular findings of glaucoma, dilated episcleral vessels, and abnormal appearance of the choroidal plexus. In this scenario, the location of the port-wine stain is based on facial venous communication and drainage patterns, rather than any association with the trigeminal nerve. Indeed, port-wine stains often are not confined to areas of innervation of the trigeminal nerve. Instead, venous drainage patterns of the upper face may be coincidentally related to the branches of the trigeminal nerve.

Given that SWS is a sporadic disorder with focal cutaneous findings, mosaicism with a somatic mutation is speculated to be the cause. In certain cases of SWS, genetic abnormalities have been seen only in the abnormal tissues. However, a discussion of the various genetic possibilities is beyond the scope of this text.

Calcifications of the leptomeningeal angiomatosis and underlying tissue is a typical radiologic feature seen in SWS, particularly as the disease progresses. Microscopic calcifications can be seen in the brain parenchyma, and deposited on arteries and veins in histologic samples. This calcification may be related to anoxia or possibly is a consequence of increased blood-brain barrier permeability.

Affected areas of the brain can show atrophy, and pathologic samples of brain tissue have shown reduced number of neurons with gliosis as well as cortical dysgenesis. Tissue hypoxia and ischemia has been presumed to account for these features. Blood flow to affected brain areas during seizures is impaired in SWS, and does not show the same elevation in flow which is typically seen with seizures in others. This failure to effectively increase perfusion during the seizure, when the brain is metabolically more active, is a likely cause of the stroke-like episodes seen in SWS, where seizures can precipitate a localized ischemic event leading to long-term or even permanent new functional impairment such as hemiparesis, cognitive decline, and visual deficits.

How do these pathogens/genes/exposures cause the disease?

N/A

Other clinical manifestations that might help with diagnosis and management

N/A

What complications might you expect from the disease or treatment of the disease?

N/A

Are additional laboratory studies available; even some that are not widely available?

Although there are some genetic mutations which have been reported to occur in the abnormal tissues in patients with SWS, there are no laboratory or genetic tests that will aid in the diagnosis, or help to direct treatment.

How can Sturge-Weber syndrome be prevented?

As an entirely sporadically occurring disorder, there are currently no known measures that will prevent SWS.

What is the evidence?

SWS is a rare disorder with a wide variation in clinical presentations, natural history, and outcomes. Thus, many treatments are based on expert opinion, case series, and retrospective studies. The evidence for some treatment options has been discussed earlier. Below is a list of the references cited above, as well as review articles and other papers of interest with additional information.

[References are in the order mentioned in the text, with the exception of an additional reference at the end that is not cited in the text.]

Ch'ng, S, Tan, ST. "Facial port-wine stains - clinical stratification and risks of neuro-ocular involvement". J Plast Reconstr Aesthet Surg. vol. 61. 2008. pp. 889-93.

Evaluated 158 consecutive patients with port-wine stains and assessed risk of ocular and neurologic complications. Adds to evidence that only those with V1 distribution port-wine stains are at risk.

Tallman, B, Tan, OT, Morelli, JG. "Location of port-wine stains and the likelihood of ophthalmic and/or central nervous system complications". Pediatrics. vol. 87. 1991. pp. 323-7.

Comi, AM. "Presentation, diagnosis, pathophysiology, and treatment of the neurological features of Sturge-Weber syndrome". Neurologist. vol. 17. 2011. pp. 179-84.

Recent review of SWS by Anne Comi who has become one of the leading experts on SWS. This review addresses many aspects of SWS including pathogenesis and treatment.

Comi, AM. "Update on Sturge-Weber syndrome: diagnosis, treatment, quantitative measures, and controversies". Lymphat Res Biol. vol. 5. 2007. pp. 257-64.

In addition to a review of the evidence, Dr. Comi includes advice on many practical issues based on her personal experience. For an additional review with helpful references, please see:

Kossoff, EH, Buck, C, Freeman, JM. "Outcomes of 32 hemispherectomies for Sturge-Weber syndrome worldwide". Neurology. vol. 59. 2002. pp. 1735-8.

Questionnaire-based, suggesting that the majority of patients with SWS who undergo hemispherectomies will become seizure-free.

Bourgeois, M, Crimmins, DW, de Oliveira, RS. "Surgical treatment of epilepsy in Sturge-Weber syndrome in children". J Neurosurg. vol. 106. 2007. pp. 20-8.

Retrospective study evaluating outcomes in 27 children with SWS who underwent surgical resection due to seizures. Authors suggest that earlier surgery leads to improved developmental outcomes. But see next reference.

Carson, BS, Javedan, SP, Freeman, JM. "Hemispherectomy: a hemidecortication approach and review of 52 cases". J Neurosurg. vol. 84. 1996. pp. 903-11.

Retrospective study evaluating the outcomes of 52 hemispherectomies in SWS which found that earlier surgeries did not improve developmental outcomes.

Bay, MJ, Kossoff, EH, Lehmann, CU. "Survey of aspirin use in Sturge-Weber syndrome". J Child Neurol. vol. 26. 2011. pp. 692-702.

Internet-based survey of patients with SWS suggesting that aspirin use is safe and reduces frequency of seizure- and stroke-like episodes.

Khaier, A, Nischal, KK, Espinosa, M. "Periocular port wine stain: the great Ormond Street Hospital experience". Ophthalmology. vol. 118. 2011. pp. 2274-8.

Retrospective case-control study of glaucoma risk in 216 patients with facial port-wine stain.

Lewis, KS. "Pediatric headache". Semin Pediatr Neurol. vol. 17. 2010. pp. 224-9.

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