Sturge-Weber Syndrome Patients Research Articles

Sturge-Weber Syndrome. Study of 55 Patients

To review the clinical and neuroimaging features of a large series of patients with Sturge-Weber syndrome (SWS) seen over a 40-year period. Fifty-five patients with SWS (30 males and 25 females), were studied between 1965 and 2004. Results of neurological and ophthalmological examinations, electroencephalographic, and neuroimaging studies were reviewed. All patients were seen by one of the authors (I. P-C). Epilepsy, hemiparesis, mental retardation and ocular problems were the most frequent and severe features of patients with Sturge-Weber syndrome in this series. The facial nevus flammeus was unilateral in 35 (63.5%) patients, bilateral in 17 (31%) and absent in 3 (5.5%) of the patients with leptomeningeal angiomas. Seven (41%) of the 17 patients with bilateral nevus flammeus had unilateral leptomeningeal angiomas. Seizures occurred in 47 patients (85.5%). Complete seizure control was obtained in 20 patients (42.5%), but in 2 of these 20 patients seizures were controlled only after lobectomy. All patients with unilateral or bilateral upper eyelid nevus flammeus had ipsilateral, unilateral or bilateral choroid-retinal angiomas. Only 20 (36%) of the 55 patients had low-normal or borderline intelligence (IQs < 70). No relationship was observed between the size of the facial nevus flammeus and the severity of the brain lesion. Epilepsy, hemiparesis, mental retardation and ocular problems were the most frequent and severe features of patients with Sturge-Weber syndrome in this series. Cerebral lesions followed a progressive course during early childhood, but not later. Early surgical treatment controlled the seizures but other neurological problems such as hemiparesis and intellectual deficits showed a less satisfactory response. Early onset of seizures and poor response to medical treatment, bilateral cerebral involvement and unilateral severe lesions were indicative of a poor prognosis. Limited intelligence and social skills, poor aesthetic appearance and seizures complicated the integration of SWS patients. These features must be addressed in order for the patients improve social interactions, obtain gainful employment and achieve a better quality of life.

Spontaneous obliteration of MRI-silent cerebral angiomatosis revealed by CT angiography in a patient with Sturge–Weber syndrome

Type I Sturge-Weber syndrome (SWS) is a neurocutaneous syndrome characterized by facial port wine stain and ipsilateral leptomeningeal angiomatosis. It is commonly complicated by glaucoma and neurological disturbances including seizures, hemiparesis, transient stroke-like deficits, and behavioral problems. Gadolinium-enhanced MRI is the study of choice for demonstrating the leptomeningeal angiomatosis, and is particularly useful for making the diagnosis. Cerebral hematoma and spontaneous obliteration of cerebral angiomatosis have never been reported in SWS. We describe a patient with type I SWS in which a hemorrhage in the left temporal lobe was caused by an underlying angiomatosis. No arteriovenous malformations were detected by brain CT or gadolinium-enhanced MRI, whereas a small angiomatous nidus draining into an ectasic venous collector near the hematoma was disclosed by brain CT angiography. Carotid angiography, performed 3 years after the hemorrhage, demonstrated the spontaneous obliteration of the angioma. This description expands the phenotypic spectrum of type I SWS in which the occurrence of cerebral hemorrhage and MRI-silent cerebral angiomatosis should be included, and emphasizes the need of performing a brain CT angiography in SWS patients whose routine neuroimaging studies fail to detect potentially harmful vessel malformation.

Self-Reported Treatment Patterns in Patients With Sturge-Weber Syndrome and Migraines

Migraine is common in patients with Sturge-Weber syndrome, yet treatment options are poorly described. An Internet-based questionnaire was completed anonymously by 104 Sturge-Weber syndrome patients, 74 of whom reported experiencing migraines (median age, 25 years; range, 3-64 years). Sixteen (22%) subjects self-reported trying triptans. Five of 12 (42%) describing triptan response believed they were very efficacious (median time of onset of 26 minutes), compared to 13 of 65 (20%) using over-the-counter analgesics (P = .08). Eighty-eight percent (14/16) of triptan users self-reported that when they do not use medications, migraines had a moderate to severe impact on their quality of life; however, while taking triptans, only 50% (7/14) of users reported such an impact (P = .03). Two patients using triptans reported transient unilateral weakness. Of the 26 patients (35%) who received daily preventative medications, 80% experienced improved quality of life. In addition, only 10 of 24 (42%) reported a significant negative impact of migraines on quality of life with daily preventative use, compared to 22 of 26 (85%) without their use (P = .002). Sturge-Weber syndrome patients with migraines are using triptans and preventative agents and self-reporting good efficacy. The small sample size precludes any safety analysis, however, and future prospective trials of both treatment options are needed.

Natural History and Magnetic Resonance Imaging Follow-up in 9 Sturge-Weber Syndrome Patients and Clinical Correlation

The natural history of Sturge-Weber Syndrome is variable where some patients have refractory epilepsy and persistent neurologic deficits while others do well. Also, evolution of MRI abnormalities is largely unknown. This long-term follow-up study tries to address these two issues. This retrospective and later prospective study followed 9 children with confirmed SWS. Clinical details of seizures, stroke-like episodes, neurologic and developmental deficits were ascertained specifically. Patients were divided into those with onset below or after 6 months of age for analysis. Disease was classified as active or inactive and correlations were made with the use of aspirin. All past, as well as prospectively acquired imaging was reviewed by two independent blinded neuroradiologists and the images were analysed as ictal (temporally related to seizure/stroke-like event) or interictal. Degree and extent of leptomeningeal enhancement was specifically looked for. Four boys and five girls were followed up for a mean of 6.1 years. Disease activity subsided in 8/9. Early-onset patients had a severe early course with significant residual deficits while late-onset patients did uniformly well. In 6 patients where aspirin was used, a stable course ensued. There was a significant increase in degree/extent of leptomeningeal enhancement during an ictus which returned to the baseline in the interictal state in all 7 patients where both images were available. Focal cerebral atrophy worsened in early-onset cases. In conclusion, SWS patients with onset of seizures/stroke-like events before 6 months of age seem to do worse with a severe early course and persistent neurologic deficits. However the course stabilizes after 5 years of age in most. Late-onset SWS patients have a benign course. Aspirin use is associated with a stable course though further studies are needed. The leptomeningeal enhancement appears to increase during acute events before returning to baseline suggesting that extent of the disease is probably best judged during the interictal state.

Upregulation of Hypoxia-Inducible Factor (HIF)-1α and HIF-2α in Leptomeningeal Vascular Malformations of Sturge-Weber Syndrome

Cutaneous and leptomeningeal vascular malformations are hallmarks of the Sturge-Weber Syndrome (SWS), resulting in chronic ischemic tissue damage. The mechanisms underlying the pathobiology of these progressive lesions are unknown. Aberrant expression of angiogenic factors has been implicated in the genesis and maintenance of vascular malformations. To assess the role of angiogenesis in SWS vascular lesions we determined the expression of key angiogenic factors by immunohistochemistry and in situ hybridization in 8 SWS patients (age: 8 months to 18 years). We observed increased expression of vascular endothelial growth factor (VEGF), its cognate receptors VEGFR-1, VEGFR-2, and neuropilin (NP)-1 as well as Tie2 in leptomeningeal SWS blood vessels. Intriguingly, these factors are known to be transcriptionally induced by hypoxia-inducible factor (HIF). The HIF system has emerged as the key regulatory system of responses to hypoxia. Immunohistochemical analysis demonstrated markedly elevated nuclear HIF-1alpha and HIF-2alpha protein levels in SWS vessels. Concomitantly, SWS vessels revealed signs of enhanced endothelial cell (EC) turnover as evidenced by increased EC proliferation and apoptosis. Thus, in terms of angiogenesis, vascular malformations in SWS are not static lesions but constitute dynamic structures. Our observation of a dysregulated HIF-alpha expression in SWS vessels are in agreement with recent findings that EC-specific HIF activation provides a setting which supports and sustains angiogenesis and could be of potential use for developing therapeutic strategies to treat these currently incurable lesions.

Clinical courses of 12 Sturge-Weber syndrome patients and evaluation of neurologic therapy

Clinical courses of 12 Sturge-Weber syndrome patients and evaluation of neurologic therapy

Analysis of Surgical and Medical Management of Glaucoma in Sturge-Weber Syndrome

Management of glaucoma associated with Sturge-Weber syndrome (SWS) is difficult. The authors reviewed 36 eyes of 30 SWS patients with either early or late-onset glaucoma with a mean follow-up of 122 months (range, 24-253 months). Intervals between required surgical or medical interventions were analyzed. Intervention was attributed to elevated intraocular pressure (IOP) in 55% of cases and disc change in 45%. Median stable postoperative interval with goniotomy was 12 months; with trabeculotomy, 21 months; with trabeculectomy, 34 months; with argon laser trabeculoplasty, 25 months; and with medications, 57 months. Survival analysis shows statistically significant differences between goniotomy and medications. Intraoperative choroidal expansions developed in 24% of cases receiving a trabeculectomy, and none developed with either goniotomy or trabeculotomy.