Brain Involvement in Sturge-Weber

Sometimes early handedness before 1 year of life, or a visual gaze preference that looks as if the child is gazing at people with his or her head turned to one side, may be an important sign that a young child has Sturge-Weber syndrome brain involvement. Parents have reported bringing these clues to the attention of their pediatrician, only to be told that everything is okay. More commonly, these infants present with seizures, but these can be just very subtle twitching in the fingers and toes. Focal seizures, strokes, and strokelike episodes, however, can play an important role in the identification of this relatively rare congenital disorder and certainly play a major role in its management. Physicians have conventionally considered the possibility of Sturge-Weber syndrome (SWS) in neonates born with a pink to dark red port-wine birthmark, typically located on one or both sides of the forehead or upper eye. SWS also is associated with vascular malformations of the eye, which can result in increased eye pressure (glaucoma) and abnormal blood vessels of the brain (leptomeningeal angioma). These malformations typically occur on the same side of the body as the birthmark. However, not all of these structures are involved in neonates with SWS. Moreover, port-wine birthmarks occur in 3 per 1,000 live births. Approximately 15%-35% of children with a facial portwine stain that involves the forehead or upper eyelid also have brain involvement with SWS. Population-based data are lacking for how many people have SWS, but it is thought to be congenital and to occur sporadically in about 1 in 20,000 live births. Once a pediatrician suspects SWS, early consultations should be held with an ophthalmologist, a dermatologist, and a neurologist. A diagnosis of brain involvement is made using contrast-enhanced MRI and head CT. But the early diagnosis and exclusion of SWS is hampered by the low sensitivity of standard imaging in young asymptomatic infants. Most MRIs performed at birth or soon afterward are normal, a result that requires repeated scans during the first years of life, each with the infant or child under sedation. To avoid repeated imaging studies, investigators at the Kennedy Krieger Institute have been evaluating quantitative EEG as a noninvasive screening tool to identify changes in brain function that would indicate the need for a contrast-enhanced MRI in asymptomatic children who are born with a facial portwine birthmark. Our studies have shown a decrease in total EEG power on the affected side that correlated strongly with neurologic clinical severity scores and MRI asymmetry scores. Since we last reported on this topic in this column (PEDIATRIC NEWS, November 2007, p. 38), we have developed a new quantitative EEG metric in 10 infants with port-wine birthmarks with or without brain involvement, and have validated it in another 9 with 100% sensitivity and specificity in identifying babies with brain involvement. This study is now enrolling outside patients with EEGs. Interested physicians can contact me ([email protected]) for additional information. Once a diagnosis of SWS is made, the mainstay of treatment includes stroke prevention and aggressive treatment of seizures. Although a single prospective case-controlled study showed a trend for mildly improved cognitive outcome with presymptomatic treatment with phenobarbital, we do not recommend presymptomatic treatment with an oral anticonvulsant. The reason is that there is no way to predict who’ll have their first seizure early on and who won’t have any seizures until 2-3 years of age. We have offered low-dose aspirin presymptomatically, and this approach is currently being studied. Approximately 75% of SWS patients who are affected with unilateral brain involvement will have seizures, whereas 95% or more with bilateral brain involvement will have epilepsy. Progression of neurologic deficits occurs in some patients, but there is a great deal of variability. Neurologic deterioration is common in SWS, although about half of patients have a relatively stable course. Case series, SPECT (single-photon emission computed tomography) studies, and unpublished observations suggest that long or repetitive seizures in patients with SWS are associated with stroke and strokelike episodes and can injure the brain. Long-term control of seizures is associated with improvement of both cerebral metabolic abnormalities and neurologic impairments, such as hemiparesis severity. For these reasons, we advocate an aggressive approach to seizure management in patients with SWS (Expert Rev. Neurother. 2007;7:951-6). All families of infants older than 3 months of age with a facial port-wine stain are given rectal diazepam (Diastat) for emergency use during a seizure, and are instructed to develop an action plan should a seizure occur. Seizure onset, which typically presents as status epilepticus, is treated with hospitalization and IV anticonvulsants such as phenobarbital or fosphenytoin for 1-2 weeks, while the chronic anticonvulsant is initiated. Once the seizure is terminated, we recommend rapid escalation of longacting anticonvulsant(s) to a dose in the moderate to high range. We typically use oxcarbazepine as our first-line chronic anticonvulsant and aim for dosing at about 40 mg/kg per day. Short-term side effects, however, can be increased with rapid escalation. This approach is different from general recommendations that suggest waiting until after a second seizure to initiate chronic anticonvulsants. Although the long-term outcome of our approach is not yet known, we believe that taking a more aggressive approach allows us to gain and maintain seizure control in most children, and thereby to prevent or ameliorate neurologic deterioration. The important thing for pediatricians who treat children with SWS and a history of seizure is to provide close followup to ensure that the anticonvulsant dosage is increased periodically to reflect the child’s ongoing weight gain. Pediatricians should weigh infants every 3 months and adjust the dose upward to maintain the same moderate to high mg/kg dose. Aggressive maintenance of dose for weight gain should be continued through childhood until the decision is made to wean the child off the medication. Controversy also exists over the use of low-dose aspirin to prevent strokes. Data from a randomized trial that addressed this fundamental issue are not yet available, although a small study suggested that low-dose aspirin may reduce the frequency of strokelike episodes with SWS. A recently completed survey conducted by Kennedy Krieger in 100 patients with SWS revealed that one-third had been on or were currently on low-dose aspirin, and that its use appeared to decrease the frequency and severity of seizures. No serious health or life-threatening issues were reported. The most common side effect was an increase in nosebleeds or gum bleeding that did not require the aspirin discontinuation. We will recommend aspirin doses of 3-5 mg/kg per day, but only after discussing the risks and benefits with parents. Because migraines may trigger strokelike episodes and seizures, we aggressively treat migraines in children with SWS by using preventive medications such as Periactin (cyproheptadine), gabapentin, topiramate, and valproic acid. Good hydration and regular sleep also are emphasized, as poor hydration and sleep hygiene also can trigger migraines. ■