Urine vascular biomarkers in Sturge-Weber syndrome.

Sturge-Weber syndrome (SWS) consists of a capillary-venous vascular malformation of the brain, skin and eye. Urine vascular biomarkers have been demonstrated to be abnormal in other vascular anomalies and to correlate with clinical severity and progression. The current study investigated the use of urinary matrix metalloproteinase (MMP)-2, MMP-9, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) levels to non-invasively monitor the progression of SWS. Fifty-four urine samples were collected from patients seen at the Hunter Nelson Sturge-Weber Center at Kennedy Krieger Institute. Urine was analyzed for MMP-2, MMP-9, VEGF and bFGF levels and correlated with clinical outcome at the time of urine collection (n = 48) and 1 year following urine collection (n = 22). Analysis revealed that MMP-2 (p = 0.033) and MMP-9 (p = 0.010) were significantly more likely to be present in the urine of SWS subjects compared to controls and that bFGF was significantly more likely to be present at abnormal levels (p = 0.005). MMP-2 correlated with a more severe clinical score at the time of urine collection, while both MMP-2 and MMP-9 levels correlated with greater disease severity at time of collection. bFGF levels correlated with improved clinical score 1 year after urine collection. These results suggest that MMP-2 and MMP-9 levels may be useful in assessing SWS progression, as well as indicating which patients might benefit from more aggressive treatment, while bFGF levels may be useful in judging the efficacy of neurologic treatment in SWS.

Anticonvulsant Efficacy in Sturge-Weber Syndrome.

OBJECTIVE: We analyzed individuals with epilepsy due to Sturge-Weber syndrome to determine which anticonvulsants provided optimal seizure control and which resulted in the fewest side effects. METHODS: One-hundred-eight records from a single center were retrospectively analyzed for Sturge-Weber syndrome brain involvement, epilepsy, Sturge-Weber syndrome neuroscores, and currently used anticonvulsants. RESULTS: Of the fourteen anticonvulsants that had been employed, the most often used agents were oxcarbazepine or carbamazepine, and levetiracetam. Individuals whose seizures at the most recent visit were fully controlled (seizure-free) for 6 months or longer were more likely to have ever tried, or currently used, oxcarbazepine or carbamazepine than those with uncontrolled seizures. Thirty-nine of 69 individuals (56.5%) were seizure-free with oxcarbazepine or carbamazepine history versus 11 of 35 individuals (31.4%) who had not taken these agents (P < 0.05); 38 of 62 patients (61.3%) were seizure-free while currently taking these anticonvulsants versus 12 of 42 (28.6%) not taking them (P < 0.01). Patients with seizure control for 6 months or longer were less likely to have ever tried, or to currently be taking, levetiracetam than those without control. Sixteen of 56 individuals (28.6%) were seizure-free with levetiracetam history versus 34 of 48 (70.8%) without it (P < 0.001); 14 of 43 individuals (32.6%) were seizure-free and currently taking levetiracetam versus 36 of 61 (59.0%) not taking it (P < 0.01). When topiramate was added as second-line medication, five of nine patients (55.6%) experienced decreased seizure severity, and worsening of glaucoma was not reported. CONCLUSIONS: Carbamazepine and oxcarbazepine were associated with better seizure control than levetiracetam in this Sturge-Weber syndrome cohort and so may be preferred as the initial therapy. When used as adjunctive therapy, topiramate was effective in this limited analysis without a clear increased incidence of glaucoma.

EEG evolution in Sturge-Weber syndrome.

The EEG in Sturge-Weber syndrome (SWS) was theorized over 50 years ago as changing over time from normality to focal asymmetry to lastly epileptiform. We sought to validate these findings in a larger cohort today. Children with confirmed SWS and routine EEG at our center were evaluated retrospectively. An EEG score (0-3) was created and linked to patient current age, overall neurologic function, and seizure frequency. Eighty-one EEGs from 44 patients with SWS (mean age 2.0 years (range: 0.2-37.9 years)) were evaluated and assigned an EEG score. The mean age for patients with an EEG score of 0-1 (normal or focal slowing) was 3.2 years (SEM 0.6), whereas those with an EEG score of 2-3 (focal sharp waves or frequent spike-wave bursts) was 8.7 years (SEM 1.7) (p=0.006). There was no correlation between the EEG score and either the SWS overall neuroscore or seizure subscore (measuring frequency). The EEG in patients with SWS does appear to evolve over time, becoming more abnormal with more frequent epileptiform activity, as suspected in smaller studies decades ago. This progressive change, however, did not correlate with the child's neurologic function or seizure frequency.

Sturge-weber syndrome.

OPINION STATEMENT: We try to see the babies prior to the onset of symptoms so that their parents can receive anticipatory guidance regarding seizures and how to recognize and respond to them and so that proper referrals to ophthalmology can be made. If there is any concern on history, exam, or EEG then we obtain a magnetic resonance imaging (MRI) with contrast. If presymptomatic diagnosis of brain involvement is made then treatment with low-dose aspirin is offered and if the brain involvement is extensively bilateral then an anticonvulsant such as levetiracetam is offered as well. Seizures are treated aggressively with a goal of obtaining and maintaining complete seizure suppression as much as possible often with a combination of low-dose aspirin and two anticonvulsants such as levetiracetam and oxcarbazepine. For many patients, this will provide adequate control of their seizures and stroke-like episodes. If the patient fails medical management and seizures are regular and accompanied by plateaued development, significant hemiparesis and visual field deficit and the patient is unilaterally involved and a surgical candidate then surgical management is urged. When the seizures are less regular, little or no hemiparesis or visual field deficit exist, and development is reasonable then this decision is more difficult. For bilaterally involved patients surgery is usually not a good option unless seizures are very severe and mostly coming from one side. Other therapeutic options include the ketogenic/Atkins diet and vagal nerve stimulator although in our experience these usually do not result in cessation of seizures. Endocrine problems occur with increased frequency and must be treated when they are present. The recent discovery of the somatic mutation causing Sturge-Weber syndrome holds promise for new treatment options in the future.