Studies to improve clinical care of Sturge-Weber Syndrome:
Harmon KA, Day AM, Hammill AM, Pinto AL, McCulloch CE, Comi AM; National Institutes of Health Rare Disease Clinical Research Consortium (RDCRN) Brain and Vascular Malformation Consortium (BVMC) SWS Investigator Group. Quality of Life in Children With Sturge-Weber Syndrome. Pediatr Neurol. 2019 Dec;101:26-32.
Aim: We assessed the utilization of the National Institutes of Health Quality of Life in Neurological Disorders (Neuro-QoL) in pediatric patients with Sturge-Weber syndrome, a rare neurovascular disorder which frequently results in seizures, brain atrophy, calcification, and a range of neurological impairments.
Methods: Subjects were seen clinically and consented for research. All 22 patients filled out the Pediatric Neuro-QoL. The Neuro-QoL subscores were converted to T-scores to compare with the referenced control population. Twenty-one participants also filled out the Brain Vascular Malformation Consortium Database Questionnaire containing data pertaining to Sturge-Weber syndrome-related medical history, medications, comorbidities, and family history. All data were analyzed with a significance threshold of P < 0.05.
Results: Cognitive function quality of life was significantly lower (P < 0.001) in pediatric patients with Sturge-Weber syndrome compared with referenced control subjects. Male gender (P = 0.02) was associated with lower cognitive function Neuro-QoL. The extent of skin (R = -0.46, P = 0.04), total eyelid port-wine birthmark (R = -0.56, P = 0.007), eye (R = -0.58, P = 0.005), and total Sturge-Weber syndrome involvement (R = -0.63, P = 0.002) were negatively correlated with cognitive function Neuro-QoL. A younger age at seizure onset was associated with lower cognitive function Neuro-QoL (hazard ratio = 0.90, P = 0.004) even after controlling for extent of brain, skin, or eye involvement. Antidepressant use was associated with lower cognitive function Neuro-QoL (P = 0.005), and cognitive function Neuro-QoL was negatively correlated with depression Neuro-QoL; however, after adjusting for depression this relationship was no longer significant.
Conclusions: The results suggest targeting cognitive function Neuro-QoL in treatment trials and reiterate the prognostic value of early seizure onset. In addition, sex-related differences were noted, which should be further studied.
Sebold AJ, Ahmed AS, Ryan TC, Cohen BA, Jampel HD, Suskauer SJ, Zabel TA, Comi AM, Rybczynski S. Suicide Screening in Sturge-Weber Syndrome: An Important Issue in Need of Further Study. Pediatr Neurol. 2020 Sep;110:80-86.
Background: Sturge-Weber syndrome is a neurocutaneous disorder associated with epilepsy, glaucoma, cognitive impairments, and a port-wine birthmark. Although individuals with Sturge-Weber syndrome are vulnerable to known risk factors for suicide, including chronic illness and physical differences (port-wine birthmark), frequency of suicidal ideation and attempts, and the clinical factors associated with suicide risk, in patients with Sturge-Weber syndrome is unknown.
Methods: As a part of routine hospital practice, all outpatients aged eight years and older underwent suicide risk screening during nursing triage using a standardized suicide screening tool. Suicide risk screening results, demographic variables, and medical history (as available) for patients with Sturge-Weber syndrome (N = 34; median age = 15.5; range = 8 to 47 years, 44% male) and other neurological conditions seen at the same institution (N = 369; median age = 14; range = 8 to 78 years, 66% male) were used for retrospective within- and between-group analysis.
Results: In the combined sample of Sturge-Weber syndrome and neurologically involved patients, a positive suicide risk screen was related to Sturge-Weber syndrome diagnosis (P = 0.043); analysis by sex showed increased risk of Sturge-Weber syndrome diagnosis in males (P = 0.008), but not in females. Within the Sturge-Weber syndrome group, use of a selective serotonin reuptake inhibitor (P = 0.019) was related to a positive risk screen.
Conclusion: People with Sturge-Weber syndrome may be at greater risk of suicidal thoughts or behaviors than those with other neurological conditions. Further study of suicide risk in patients with Sturge-Weber syndrome is needed.
Sebold AJ, Day AM, Ewen J, Adamek J, Byars A, Cohen B, Kossoff EH, Mizuno T, Ryan M, Sievers J, Smegal L, Suskauer SJ, Thomas C, Vinks A, Zabel TA, Hammill AM, Comi AM. Sirolimus Treatment in Sturge-Weber Syndrome. Pediatr Neurol. 2021 Feb;115:29-40.
Background: Sturge-Weber syndrome is a rare neurovascular disorder associated with capillary malformation, seizures, cognitive impairments, and stroke-like episodes (SLEs), arising from a somatic activating mutation in GNAQ. Studies suggest this mutation may cause hyperactivation of the mammalian target of rapamycin pathway. Sirolimus is an mammalian target of rapamycin inhibitor studied in other vascular anomalies and a potentially promising therapy in Sturge-Weber syndrome.
Methods: Ten patients with Sturge-Weber syndrome brain involvement and cognitive impairments were enrolled. Oral sirolimus was taken for six months (maximum dose: 2 mg/day, target trough level: 4-6 ng/mL). Neuropsychological testing, electroencephalography, and port-wine score were performed at baseline and after six months on sirolimus. Neuroquality of life, adverse events, and Sturge-Weber Syndrome Neurological Score (neuroscore) were recorded at each visit.
Results: Sirolimus was generally well tolerated; one subject withdrew early. Adverse events considered related to sirolimus were mostly (15/16) grade 1. A significant increase in processing speed was seen in the overall group (P = 0.031); five of nine patients with available data demonstrated statistically rare improvement in processing speed. Improvements were seen in the neuroquality of life subscales measuring anger (P = 0.011), cognitive function (P = 0.015), and depression (P = 0.046). Three subjects experiencing SLEs before and during the study reported shortened recovery times while on sirolimus.
Conclusions: Sirolimus was well tolerated in individuals with Sturge-Weber syndrome and may be beneficial for cognitive impairments, especially in patients with impaired processing speed or a history of SLE. A future, randomized, placebo-controlled trial of sirolimus in patients with Sturge-Weber syndrome is needed to further understand these potentially beneficial effects.
Smegal LF, Sebold AJ, Hammill AM, Juhász C, Lo WD, Miles DK, Wilfong AA, Levin AV, Fisher B, Ball KL, Pinto AL, Comi AM; National Institutes of Health Sponsor: Rare Disease Clinical Research Consortium (RDCRN) Brain Vascular Malformation Consortium (BVMC) SWS Investigator Group. Multicenter Research Data of Epilepsy Management in Patients With Sturge-Weber Syndrome. Pediatr Neurol. 2021 Jun;119:3-10.
Abstract: Background: Epilepsy in typical Sturge-Weber syndrome (SWS) is common, and many questions remain regarding the treatment outcomes. We analyzed a large multicenter database with focus on neurological drug treatment in different demographic and SWS characteristic groups.
Methods: A total of 268 patients with brain involvement and a history of seizures were selected from a research data registry generated from a multicenter cross-sectional questionnaire. We examined associations between medication use and binary variables such as sex, ethnicity, and brain, skin, and eye involvement laterality. We analyzed group differences in mean number of antiseizure medications and age at diagnosis, enrollment, and seizure onset and examined differences in median SWS neurological scores in groups of interest.
Results: The most frequently used medications were levetiracetam (48.1%), low-dose aspirin (44.8%), oxcarbazepine (39.9%), and phenobarbital (14.9%). Lamotrigine was more frequently used in adults than in children (P = 0.001). History of neurosurgery was associated with no current antiseizure medication use (P = 0.001), whereas bilateral brain involvement and family history of seizures were associated with using a higher number of antiseizure medications (P = 0.002, P = 0.027, respectively). Subjects with bilateral brain involvement and early seizure onset were associated with using a higher number of antiseizure medications (P = 0.002) and phenobarbital use (0.003).
Conclusions: Levetiracetam, low-dose aspirin, and oxcarbazepine were the most frequently used medications. More severely affected patients were frequently on a greater number of antiseizure medications. Surgery for epilepsy was associated with the ability to discontinue antiseizure medication. Longitudinal studies are needed to further investigate medication use in patients with SWS.
Wellman, R. J., Cho, S. B., Singh, P., Tune, M., Pardo, C. A., Comi, A. M., & BVMC Sturge–Weber syndrome Project Workgroup. (2018). Gαq and hyper-phosphorylated ERK expression in Sturge–Weber syndrome leptomeningeal blood vessel endothelial cells. Vascular Medicine, 1358863X18786068.
Hyperactivating mutations in GNAQ have been discovered in a growing number of disorders including uveal melanoma, phakomatosis pigmentovascularis, port-wine birthmarks and Sturge–Weber syndrome (SWS).1,2 SWS, a sporadic neurocutaneous syndrome, is associated with facial port-wine birthmarks (PWBs), glaucoma, and a leptomeningeal angioma involving the brain. Patients present with seizures, stroke-like episodes, and cognitive impairment. The leptomeningeal vascular malformation consists of an increased number of tortuous abnormal blood vessels. GNAQ codes for Gαq, part of the trimeric G protein complex associated with several G protein-coupled receptors. The R183Q mutation in GNAQ, which causes about 85% of SWS,3 is predicted to impair auto-hydrolysis and deactivation of Gαq, and to cause constitutive hyperactivation of downstream pathways. Potential hyperactivated pathways include the Ras-Raf-MEK-ERK,1 mTOR,4 and YAP-HIPPO pathways.5 The GNAQ mutation has been shown to be enriched in the endothelial cells of SWS leptomeningeal/ superficial cortical brain samples.6 We sought to determine the expression of Gαq and downstream phosphorylated extracellular signal-regulated kinase (p-ERK) in human SWS brain tissue to better understand how the somatic mutation results in a vascular malformation. CD34+ was selected as a marker of endothelial cellsbecause, when labeling the inner layer of capillary-venous vessels, this marker is specific for endothelial cells, it does not also label other mature hematopoietic cells, and its role in differentiation, adhesion and migration is of potential interest in SWS angiogenesis.
Stafstrom, C. E., Staedtke, V., & Comi, A. M. (2017). Epilepsy Mechanisms in Neurocutaneous Disorders: Tuberous Sclerosis Complex, Neurofibromatosis Type 1, and Sturge–Weber Syndrome. Frontiers in neurology, 8, 87.
Neurocutaneous disorders are multisystem diseases affecting skin, brain, and other organs. Epilepsy is very common in the neurocutaneous disorders, affecting up to 90% of patients with tuberous sclerosis complex (TSC) and Sturge–Weber syndrome (SWS), for example. The mechanisms underlying the increased predisposition to brain hyperex-citability differ between disorders, yet some molecular pathways overlap. For instance, the mechanistic target of rapamycin (mTOR) signaling cascade plays a central role in sei-zures and epileptogenesis in numerous acquired and genetic disorders, including several neurocutaneous disorders. Potential routes for target-specific treatments are emerging as the genetic and molecular pathways involved in neurocutaneous disorders become increasingly understood. This review explores the clinical features and mechanisms of epilepsy in three common neurocutaneous disorders—TSC, neurofibromatosis type 1, and SWS.
Day AM, M. C., Hammill AM, Juhasz C, Lo W, Pinto PL, Miles D, Fisher BJ, Ball KL, Wilfong A, Levin AV, Thau AJ, Comi AM and collaborators. (2018). Physical and Family History Variables Associated with Neurologic and Cognitive Development in Sturge-Weber Syndrome. Pediatric Neurology.
Sturge-Weber syndrome (SWS) is caused by a somatic mutation in GNAQ leading to capillary-venous malformations in the brain presenting with various neurologic, ophthalmic, and cognitive symptoms of variable severity. This clinical variability makes accurate prognosis difficult. We hypothesized that greater extent of physical factors (extent of skin, eye and brain involvement), presence of possible genetic factors (gender and family history) and age of seizure onset may be associated with greater symptom severity and need for surgery in patients with SWS.
Day, A. M., Hammill, A. M., Juhász, C., Pinto, A. L., Roach, E. S., McCulloch, C. E., ... & Lawton, M. T. (2018). Hypothesis: Presymptomatic treatment of Sturge-Weber Syndrome With Aspirin and Antiepileptic Drugs May Delay Seizure Onset. Pediatric neurology.
SWS is a devastating disease with a progressive nature. Efforts should be made to identify neuroprotective interventions that could positively impact outcome in early stages of the disease. We hypothesized that low-dose antiepileptic drugs and aspirin may be effective in delaying seizure onset in SWS infants. This hypothesis is supported by lower seizure scores and older age of seizure onset in the presymptomatically treated infants. Most notably, four of the infants treated presymptomatically with antiepileptic drugs and aspirin had yet to develop seizures at ages 14 to 39 months.
Cannabidiol Treatment for Refractory Seizures in Sturge-Weber Syndrome. Kaplan EH1, Offermann EA1, Sievers JW2, Comi AM.
Dr. Comi’s study treated five patients with Sturge-Weber syndrome (SWS) with Epidiolex. Patients with SWS have abnormal blood vessels in the brain and eye and a facial port-wine birthmark. Many have hard-to-control seizures. Epidiolex is a pharmaceutical formulation of cannabidiol oil provided by GW Research as part of the FDA-approved expanded-access program for pediatric epilepsy. SWS differs from other causes of medically refractory epilepsy in that decreased blood flow to the brain can result in stroke. Preclinical studies have shown that cannabidiol can have therapeutic effects on blood vessel function.
Of the five patients treated in the study, three demonstrated a greater than 50 percent reduction in seizures for over a year, and one of these patients became seizure-free. These three individuals all had bilateral SWS brain involvement and had previously tried—with no therapeutic effect—two to seven seizure medications each. At the end of the study, the patients and their families reported improved quality of life, along with other neurologic, behavioral or mood improvements. Side effects attributed to Epidiolex were temporary and included behavioral issues, tiredness, a temporary increase in seizures and an increased aspartate aminotransferase (AST) liver function test. The authors concluded that further study of Epidiolex for SWS was warranted. Next, a multi-centered, placebo-controlled study should be done to demonstrate the effectiveness and safety of Epidiolex for the treatment of refractory seizures in SWS.
Cannabodiol has been FDA approved as a schedule five drug for treatment of seizures in Lennox-Gastaut syndrome and Dravet syndrome.
For the background story on how this study came to fruition, click here.
Post-study quotes from two participants:
“Before starting the study, Isabella was in a deep depression and having several seizures a month. After receiving Epidiolex, she is a different person. Her problem-solving skills and vocabulary have progressed tremendously. She’s happy. Her anxiety and depression are gone, and she only has one seizure a month.”
– Laurie Marconi, mother to study participant Isabella, age 21
“When we enrolled Addisyn in the study, she was on four seizure medications at maximum dosages. She was having several seizures a day and was like a zombie, barely functioning. After one dose of Epidiolex, she didn’t have any seizures. Now, she’s down to just one medication in addition to the Epidiolex, and she’s thriving.”
– Krissta Ross, mother to study participant Addisyn, age 9
Anticonvulsant Efficacy in Sturge-Weber Syndrome. Kaplan EH, Kossoff EH, Bachur CD, Gholston M, Hahn J, Widlus M, Comi AM. Pediatr Neurol. 2016; Advance online publication. doi: 10.1016/j.pediatrneurol.2015.10.015.
Patients with SWS are often prescribed one or several seizure (anticonvulsant) medications. This study examined these different anticonvulsants, their side effects and the associated clinical outcomes.
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. 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. 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. 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.
Aspirin use in Sturge-Weber syndrome: side effects and clinical outcomes. Lance EI, Sreenivasan AK, Zabel TA, Kossoff EH, Comi AM. J Child Neurol. 2013 Feb;28(2):213-8. doi: 10.1177/0883073812463607. Epub 2012 Oct 30.
This study summarized our experience with the side effects and outcomes of low-dose aspirin usage in a large number of children with Sturge-Weber syndrome suggesting that low-dose aspirin is generally safe and useful in the treatment of patients with SWS.
Sturge-Weber syndrome is a neurocutaneous disorder with skin, eye, and brain involvement. Prior series suggest about 50% of patients have seizures/neurodeterioration. Low-dose (3-5 mg/kg/d) aspirin use in this population is controversial. This study further addresses the side effects and outcomes of low-dose aspirin usage in Sturge-Weber syndrome. Fifty-eight subjects on aspirin with brain involvement were analyzed in a retrospective chart review. Charts were evaluated for brain involvement, age at first seizure, and side effects. Subjects' clinical stability was compared using neurologic scores. The majority of subjects had neurologic scores reflecting reasonable seizure control (91%), none or mild hemiparesis (57%), no vision impairment (71%), and none or mild cognitive impairment (80%). Forty-nine reported no significant side effects, and 9 reported either allergic reaction or minimal to significant bleeding on aspirin. This cohort's clinical experience adds significant support for low-dose aspirin use to optimize neurodevelopmental outcome in Sturge-Weber syndrome with minimal side effects.
Importance of utilizing a sensitive free thyroxine assay in Sturge-Weber syndrome. Siddique L, Sreenivasan A, Comi AM, Germain-Lee EL. J Child Neurol. 2013 Feb;28(2):269-74. doi: 10.1177/0883073812463606. Epub 2012 Oct 30.
This study described 5 children with Sturge-Weber syndrome on anticonvulsants suspected to have hypothyroidism and the importance of using the free T4 assay in order to accurately diagnose hypothyroidism.
Sturge-Weber syndrome has been found to result in hypothalamic-pituitary dysfunction including central hypothyroidism. Because central hypothyroidism is more prevalent in Sturge-Weber syndrome than in the general population, we routinely evaluated thyroid function. Here we describe 5 children with Sturge-Weber syndrome on anticonvulsants and diagnosed with hypothyroidism based on thyroid function testing. All 5 patients were eventually tested utilizing the more accurate free thyroxine equilibrium dialysis assay. Results indicated that only 2 of the 5 patients, who exhibited the most severe symptoms, had true hypothyroidism. This case series demonstrates the benefits of using the free thyroxine by equilibrium dialysis when testing Sturge-Weber syndrome patients on antiepileptic medications. This testing algorithm is more cost-effective and also improves the quality of care by providing an accurate diagnosis more quickly. In addition, we propose consideration of this testing method in any patient taking anticonvulsants, most notably oxcarbazepine.
A pilot study of the modified Atkins diet for Sturge-Weber syndrome. Kossoff EH, Borsage JL, Comi AM. Epilepsy Res. 2010 Dec;92(2-3):240-3.
Studied how a modified Atkins diet (MAD) as a dietary treatment for epilepsy in patients with Sturge-Weber syndrome. Theoretically is safer than the ketogenic diet for children with SWS. All children had urinary ketosis and seizure improvement, including 3 with > 50% seizure reduction.
The modified Atkins diet (MAD) is a dietary treatment for epilepsy which does not restrict fluids or calories. This theoretically makes the MAD safer than the ketogenic diet for children with Sturge-Weber syndrome (SWS). Five children aged 4-18 years with SWS and at least monthly intractable seizures were started prospectively on the MAD for 6 months. All children had urinary ketosis and seizure improvement, including 3 with > 50% seizure reduction.
Survey of aspirin use in Sturge-Weber syndrome. Bay MJ, Kossoff EH, Lehmann CU, Zabel TA, Comi AM. J Child Neurol. 2011 Jun;26(6):692-702.
Study showed a significant relative reduction in both self-reported seizure frequency and stroke-like episodes after starting aspirin. It also suggests that low-dose aspirin can be safely used in these patients.
Sturge-Weber syndrome is a rare congenital disorder. Seizures, stroke-like episodes, glaucoma, headache, and developmental delay are frequently associated features. An Internet-based questionnaire was designed to assess the frequency of use, effectiveness, and safety of aspirin treatment in Sturge-Weber syndrome. Thirty-four of 98 subjects who completed the survey reported having used aspirin. The mean number of reported stroke-like episodes was reduced from 1.1 to 0.3 per month in the year after starting aspirin (n = 26, p = .014). The median number of seizures was significantly reduced from 3 to 1 episodes per month (n = 21, p = .002). Thirty-nine percent of subjects reported a history of complications (predominantly increased bruising or gum/nose bleeding) while on aspirin; however, none reported discontinuing aspirin because of side effects. Our study showed a significant relative reduction in both self-reported seizure frequency and stroke-like episodes after starting aspirin. It also suggests that low-dose aspirin can be safely used in these patients.
Effect of a single application of pulsed dye laser treatment of port-wine birthmarks on intraocular pressure. Quan SY, Comi AM, Parsa CF, Irving ND, Krakowski AC, Cohen BA. Arch Dermatol. 2010 Sep;146(9):1015-8.
Study examined optimal timing and use of laser in the treatment of patients with or at-risk for Sturge-Weber syndrome. No evidence of worsening of eye pressures was noted immediately after laser treatments compared to just prior to the laser eye treatment.
BACKGROUND: A new pathophysiologic mechanism has been proposed that indicates that periorbital port-wine birthmarks (PWBs) serve as alternate collateral blood passageways when orbital venous drainage is impaired. The occlusion of such collateral venous channels could, therefore, potentially exacerbate impaired ocular venous flow and trigger the development or worsening of glaucoma in patients with Sturge-Weber syndrome. We investigated to what extent a single application of laser therapy, which occludes only the most superficial portions of a facial PWB, might affect intraocular pressure. Pressures before and after laser treatment were measured to determine pressure difference in 15 patients receiving laser treatment.
OBSERVATIONS: The greatest pressure differences were observed in patients with a PWB closest to the eye (P = .02). Posttreatment pressures were significantly decreased, relative to pretreatment pressures, only in patients with a PWB on the eyelid compared with patients with a facial PWB not near the eyes (2.33 vs 0.75 mm Hg; P = .004). No correlation was found between change in pressure and patient age, PWB size, or number of previous treatments.
CONCLUSIONS: A single laser application to a PWB does not appear to show a clinically relevant change in intraocular pressure. Further study is needed longitudinally in a broad range of patients.
Sturge-Weber syndrome with cerebellar involvement. Smith PM, Abdalla WM, Lin DD, Comi AM, Boltshauser E, Gailloud P, Huisman TA. J Neuroradiol. 2008. Aug 20. [Epub ahead of print]
Divisions of Interventional Neuroradiology, Johns Hopkins Hospital, Baltimore, USA.
The importance of this study is that it highlights the occurrence of lesser known cerebellar brain involvement in SWS so that this is aspect is not overlooked in patients.
Sturge-Weber syndrome is a rare neurocutaneous disorder that typically presents with angiomas involving the face, ocular choroid and ipsilateral supratentorial leptomeninges. Posterior fossa involvement is extremely rare. We present two patients with simultaneous supra- and infratentorial involvement. Magnetic resonance imaging (MRI) and digital subtracted angiography (DSA) findings are discussed.
Central hypothyroidism and Sturge-Weber syndrome. Comi AM, Bellamkonda S, Ferenc LM, Cohen BA, Germain-Lee EL. Pediatr Neurol. 2008 Jul; 39(1):58-62.
Department of Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore, Maryland 21205, USA. firstname.lastname@example.org
This paper stresses the need to test thyroid function in patients with SWS and treat deficiency if present. This problem was not previously described in the context of SWS.
Sturge-Weber syndrome is a rare disorder manifesting with a facial port-wine birthmark and a vascular malformation of the brain. Infants and children present with seizures and stroke-like episodes with focal neurologic deficits. Our previous investigations revealed that growth-hormone deficiency occurs with an increased prevalence in Sturge-Weber syndrome, presumably secondary to involvement of the hypothalamic-pituitary axis. We have continued to screen for hormonal abnormalities in patients with Sturge-Weber syndrome, specifically those from our multidisciplinary center for patients with this condition. We describe 2 children out of 83 (2.4%) with Sturge-Weber syndrome and brain involvement who were evaluated at our center and diagnosed with central hypothyroidism, based on clinical signs and laboratory findings. This prevalence is much higher than that of central hypothyroidism in the general population. Although it is well-known that anticonvulsants can lead to abnormalities in thyroid function tests, including central hypothyroidism, patients with Sturge-Weber syndrome carry the additional risk of developing hypothalamic-pituitary dysfunction, secondary to their central nervous system dysfunction. Therefore, it is important that patients with Sturge-Weber syndrome undergo routine thyroid-function testing, especially in the face of any clinical manifestations.
Sturge-Weber syndrome and epilepsy: an argument for aggressive seizure management in these patients. Comi AM. Expert Rev Neurother. 2007 Aug; 7(8):951-6.
Department of Neurology, Kennedy Krieger Institute & Johns Hopkins Medicine, Baltimore, MD, USA. email@example.com
This paper argues, based on the literature, our research, and our clinical experience that early aggressive seizure management is important to the longterm neurodevelopmental outcome in SWS.
Sturge-Weber syndrome (SWS) involves vascular malformations of the skin (facial port-wine stain), eye (glaucoma) and the brain (leptomeningeal angioma). Children born with a port-wine stain on the upper part of the face are also at risk for brain involvement. These infants and young children often develop seizures and other neurologic impairments. Progression in neurologic deficits does occur in some patients, but this is quite variable. A diagnosis of brain involvement is made with head computed tomography and contrast-enhanced MRI, but the sensitivity of standard imaging in young asymptomatic infants is low. Seizures occur in more than 75% of affected individuals. Clinical course and functional imaging suggest a role for both cerebral perfusion impairments and seizures in the development of neurologic deficits. Several controversies exist in the management of seizures and other neurologic impairments in SWS. Continued efforts are needed to develop a multicentered network for SWS clinical trials. Future research should be focused on this goal and on studies to improve our understanding of the cause(s) and molecular neuropathology of SWS.
Self-reported treatment patterns in patients with Sturge-Weber syndrome and migraines. Kossoff EH, Balasta M, Hatfield LM, Lehmann CU, Comi AM. J Child Neuro. 2007 Jun; 22(6):720-6.
Department of Neurology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA. firstname.lastname@example.org
This research highlighted several important findings including the underuse of migraine prophylactic medications and the safe effective use of triptans for migraines in some patients with SWS.
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.
Update on Sturge-Weber syndrome: diagnostic, treatment, quantitative measures, and controversies. Comi AM. Lymphat Res Biol. 2007; 5(4):257-64.
Neurology and Developmental Medicine, Kennedy Krieger Institute, Department of Neurology and Pediatrics, Johns Hopkins School of Medicine; Baltimore, MD 21205, USA. email@example.com
This review summarized the recent and evolving literature on the current and needed tools for diagnosis and monitoring in SWS, treatment trends, and highlighted key research questions and directions.
Sturge-Weber syndrome (SWS) is defined by the association of a facial capillary malformation (port-wine stain), with a vascular malformation of the eye, and/or vascular malformation of the brain (leptomeningeal angioma). Variants exist where only one of these three structures is involved with the vascular malformation. SWS occurs sporadically and is congenital. Port-wine stains occur in 3 per 1000 live births. No good population-based data exist for how many people have Sturge-Weber syndrome, however, estimates range between one in 20-50,000 live births. This review summarizes literature regarding the main features and pathophysiology of Sturge-Weber syndrome, however the cause of this syndrome remains obscure. Recent advances in neuroimaging have provided important insights into the progression of neurologic injury that occurs as a result of impaired blood flow. Important limitations exist, however, as currently the early diagnosis and exclusion of Sturge-Weber syndrome is impaired by the poor sensitivity of imaging in the newborn period and early infancy. Several important controversies complicate our ability to care for these patients and include the questions of ideal timing of surgery, whether seizures themselves contribute to the neurologic injury, and what the role of low-dose aspirin should be. This review will summarize several recent advances in our understanding of the mechanisms of brain injury in SWS, new measures for quantifying the neurologic involvement and new approaches and controversies in the management of the neurologic complications.
Myoclonic-astatic epilepsy in a child with Sturge-Weber syndrome. Ewen JB, Comi AM, Kossoff EH. Pediatr Neurol. 2007 Feb; 36(2):115-7.
Department of Neurology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA. firstname.lastname@example.org
This paper highlights the importance of being aware that patients with SWS can have generalized drop seizures that worsen with some anticonvulsants and need to be properly diagnosed with EEG and properly treated with an anticonvulsant that covers both focal and generalized seizures.
A child with Sturge-Weber syndrome and a left occipital leptomeningeal angioma developed focal seizures at 6 years of age that responded initially to oxcarbazepine. After 7 months of seizure freedom, the patient developed typical myoclonic-astatic seizures associated with generalized electrographic discharges, which worsened as oxcarbazepine was increased. The seizures and electroencephalogram improved dramatically in 3 weeks as the oxcarbazepine was withdrawn and valproic acid was initiated. This case demonstrates the importance of recognizing that children with epilepsy due to focal lesions can develop secondary bilateral synchrony that can be aggravated by medications that are effective for partial seizures. In such cases, treatment with a broad-spectrum antiepileptic may be advantageous.
Oromaxillofacial osseous abnormality in Sturge-Weber syndrome: case report and review of the literature. Lin DD, Gailloud P, McCarthy EF, Comi AM. AJNR Am J Neuroradiol. 2006 Feb; 27(2): 274-7.
Division of Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
This paper reported an unusual bony tumor of the upper jaw associated with SWS so that if this situation occurs again doctors know what to do.
We report a case of a 17-month-old child affected by Sturge-Weber syndrome who had unusually rapid overgrowth of the left frontal, temporal, orbital, and maxillary regions. CT angiography illustrated osteohypertrophy with periostitis and associated soft tissue hypertrophy directly corresponding to the distribution of the cutaneous port-wine stain. Extended maxillectomy was performed because of rapid growth and clinical debilitation, with surgical pathology revealing juvenile ossifying fibroma.
Advances in Sturge-Weber syndrome. Comi AM. Curr Opin Neurol. 2006; 19(2):124-8.
Neurology and Pediatrics, Kennedy Krieger Institute and Johns Hopkins Medicine, 707 N. Broadway, Baltimore, MD 21205, USA. email@example.com
This review article summarized recent advances in diagnosis and treatment of SWS.
PURPOSE OF REVIEW: Recent neuroimaging, clinical and molecular neuropathologic studies have provided new insights into the neurologic aspects of Sturge-Weber syndrome and are summarized here. RECENT FINDINGS: Molecular studies suggest that abnormal brain blood vessel vasoactive and extracellular matrix molecule expression, as well as aberrant brain vascular innervation, contribute to the vascular malformation and its consequences. New magnetic resonance sequences may be useful for the early diagnosis of Sturge-Weber syndrome and perfusion magnetic resonance imaging, single photon emission computed tomography imaging, and positron emission tomography imaging studies are suggesting that decreased brain blood flow combined with altered hemodynamics during prolonged seizures may contribute to the neurologic declines in Sturge-Weber syndrome. SUMMARY: Recent advances in our understanding of the neurologic issues offer promise for preventing brain injury in Sturge-Weber syndrome. More research is needed to translate advances in molecular research and neuroimaging advances into new treatment strategies for the disease.
Growth hormone deficiency in children with Sturge-Weber syndrome. Miller RS, Ball KL, Comi AM, Germain-Lee EL. Arch Dis Child. 2006 Apr;91(4):340-1
Division of Pediatric Endocrinology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
This research demonstrated for the first time that growth hormone deficiency occurs in SWS with greatly increased prevalence compared to the general population and requires treatment.
Sturge-Weber syndrome (SWS) is a disorder involving central nervous system abnormalities that may increase the risk of hypothalamic-pituitary dysfunction. Records of 19 patients with suspected growth hormone deficiency (GHD), identified from a registry of 1653 patients with SWS, were reviewed; nine patients with GHD were found.
Comorbidity of headaches and epilepsy in patients with Sturge-Weber syndrome. Kossoff EH, Hatfield LA, Ball KL, Comi AM. J Child Neurol. 2005 Aug;20(8):678-82.
Department of Neurology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA. firstname.lastname@example.org
This research showed that in older children and adults with SWS headaches are an important and undertreated neurologic problem requiring additional study and new treatment options.
Sturge-Weber syndrome is associated with leptomeningeal angioma, trigeminal port-wine stain, epilepsy, and glaucoma. Clinically, many patients with Sturge-Weber syndrome are observed to have both seizures and headaches, but this has never been described in the literature. A questionnaire was mailed to 190 patients with reported comorbid epilepsy and headache as identified by the Sturge-Weber Foundation. Sixty-eight surveys were returned anonymously; 55 reported both seizures and headaches. The median age at headache onset was 8 years, with a median of three headaches per month. Fifty-eight percent felt that headaches were an equal or greater problem. Ibuprofen and acetaminophen were the most frequently tried abortive medications; 22% had tried sumatriptan. Only 22% reported a neurologist suggesting the use of an anticonvulsant as a preventive agent. Subjects with a family history of headaches had an earlier age at headache onset (7.5 vs 11 years; P = .02), and those with a family history of seizures were more likely to report behavior problems (69% vs 33%; P = .02). Subjects reporting learning problems or hemiparesis had an earlier age at seizure onset. Migraine-like headaches can be as significant a problem as epilepsy for patients with Sturge-Weber syndrome. Despite this, triptans and prophylactic medications (including anticonvulsants) were used in less than half of the patients. Correlations of family history with both age at symptom onset and behavior problems suggest that genetic substrate could be one factor determining the variable neurologic manifestations seen in Sturge-Weber syndrome.
Outcomes of 32 hemispherectomies for Sturge-Weber syndrome worldwide. Kossoff EH, Buck C, Freeman JM. Neurology. 2002 Dec 10;59(11):1735-8.
This research indicated that hemispherectomy was effective in controlling seizures in SWS but this study did not indicate that early hemispherectomy significantly improved longterm functional outcome compared with later surgery.
BACKGROUND: Epilepsy affects 80% of patients with Sturge-Weber syndrome; the majority of seizures begin before the age of 1. When seizures are intractable to medications and unihemispheric, hemispherectomy is often advised. OBJECTIVE: To examine the natural history of patients who underwent hemispherectomy and identify the outcomes in terms of seizure reduction, cognition, and motor deficits. METHODS: A questionnaire was mailed to the parents of patients identified by the Sturge-Weber Foundation as having had a hemispherectomy between 1979 and 2001. Forty-six percent (32/70) of the parents responded. RESULTS: The mean age at onset of seizures was 4 months, and the median age at surgery was 1.2 years. Children had failed to respond to 3.7 anticonvulsants prior to surgery and averaged 387 seizures/month. Forty-seven percent had complications (e.g., hemorrhage and hypertension) in the perioperative period; however, 81% are currently seizure-free, with 53% off anticonvulsants. Hemispherectomy type (anatomic versus functional versus hemidecortication) did not influence outcome. Age at onset of seizures did not predict seizure freedom; however, an older age at hemispherectomy was positively correlated. Postoperative hemiparesis was not more severe than before surgery. Cognitive outcome was not related to the age at operation, side of operation, or seizure freedom. CONCLUSIONS: Children undergoing hemispherectomy presented at a young age and had frequent seizures for approximately 1 year but are now mostly seizure-free. Age at surgery did not have an adverse effect on either seizure or cognitive outcomes.
Sturge-Weber syndrome. Comi AM. In: Gilman, S, editor. MedLink Neurology. San Diego: MedLink Corporation. Available at MedLink 2004.
This review updated annually summarizes information on eitiology, diagnosis, treatment and monitoring of patients with SWS.
Dr. Anne Comi explains that Sturge-Weber syndrome is a neurocutaneous disorder presenting with a facial capillary malformation (port-wine birthmark), abnormal blood vessels on the surface of the brain (leptomeningeal angioma) and glaucoma. These patients frequently develop seizures, focal neurologic impairments, visual problems, and cognitive deficits. Her updated chapter summarizes recent research into the pathophysiology of this unique disorder and explains the diagnosis and treatment approaches utilized at the Sturge-Weber Syndrome Clinical Center of Excellence.
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Learn more about Completed Research Studies to:
Improve Diagnosis and Monitoring of Sturge-Weber syndrome
Understand the Pathogenesis of Sturge-Weber syndrome