Sturge-weber syndrome. Bachur CD, Comi AM. Curr Treat Options Neurol. 2013 Oct; 15(5):607-17. doi: 10.1007/s11940-013-0253-6.
Neurology and Developmental Medicine, Hugo W. Moser Research Institute at Kennedy Krieger, 801 N. Broadway, Room 553, Baltimore, MD, 21205, USA, firstname.lastname@example.org.
This manuscript summarizes the latest neurologic treatment trends and recommendations
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.
Increased choroidal thickness in patients with Sturge-Weber syndrome. Arora KS, Quigley HA, Comi AM, Miller RB, Jampel HD. JAMA Ophthalmol. 2013 Sep; 131(9):1216-9. doi: 10.1001/jamaophthalmol.2013.4044.
Glaucoma Center of Excellence, Wilmer Ophthalmological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
This study demonstrated that optical coherence tomography can quantify eye involvement with the vascular malformation in Sturge-Weber syndrome and may be useful as a biomarker in clinical care and drug trials.
IMPORTANCE: With the recent development of enhanced depth imaging spectral-domain optical coherence tomography (SD-OCT), it is now possible to measure choroidal thickness in patients with Sturge-Weber syndrome and detect abnormalities that are not visible as part of the fundus examination.
OBSERVATIONS: We were successful in imaging at least 1 eye in 12 individuals with Sturge-Weber syndrome using enhanced depth imaging SD-OCT. Eyes were defined as affected if they manifested at least one of the following: darkened choroid, glaucomatous optic nerve damage, or conjunctival hyperemia. None of the participants had a clinically visible choroidal hemangioma. The affected eyes had over twice the choroidal thickness of the unaffected eyes (mean [SD], 697  μm vs 331  μm; P = .004, determined by use of an unpaired t test). For the 6 unilaterally affected participants who had both eyes imaged, the choroidal thickness was greater in the affected eyes than in the unaffected eyes of 5 participants (mean [SD], 672  μm vs 329  μm; P = .01, determined by use of a paired t test).
CONCLUSIONS AND RELEVANCE: The advent of enhanced depth imaging SD-OCT has allowed us to quantify choroidal thickness in the posterior pole, even in eyes with a markedly thickened choroid, such as those found in individuals with Sturge-Weber syndrome. Spectral-domain OCT has a much higher resolution (5-10 μm) than B-scan ultrasonography (150 μm) and can be used to distinguish between the retina and the choroid. Furthermore, enhanced depth imaging SD-OCT can detect choroidal thickness in eyes without clinically apparent choroidal abnormalities.
Urine vascular biomarkers in Sturge-Weber syndrome. Sreenivasan AK, Bachur CD, Lanier KE, Curatolo AS, Connors SM, Moses MA, Comi AM. Vasc Med. 2013 Jun; 18(3):122-8. doi: 10.1177/1358863X13486312.
Department of Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore, Maryland 21205, USA. email@example.com
This study showed that urine biomarkers correlate with the severity of neurologic involvement in Sturge-Weber syndrome and can be developed as a biomarker for clinical care and drug trials 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.
Case Report of Subdural Hematoma in a Patient With Sturge-Weber Syndrome and Literature Review: Questions and Implications for Therapy. Lopez J, Yeom KW, Comi AM, Van Haren K. J Child Neurol. 2012 Jul 17.
Authors present a toddler with Sturge-Weber syndrome who developed a subdural hematoma in the setting of a mechanical fall with minor head trauma. This paper discusses the possible role of aspirin in contributing to, or perhaps protecting against, intracranial hemorrhage in patients with Sturge-Weber syndrome.
Neuropsychological features and risk factors in children with Sturge-Weber syndrome: four case reports. Zabel TA, Reesman J, Wodka EL, Gray R, Suskauer SJ, Turin E, Ferenc LM, Lin DD, Kossoff EH, Comi AM. Clin Neuropsychol. 2010;24(5):841-59. doi: 10.1080/13854046.2010.485133.
Four cases presented here (ages 8-9, two females) illustrate the broad range of physiologic involvement and associated neuropsychological functioning in SWS. Findings argue against the idea of a "typical" SWS neuropsychological presentation. Report highlights a preliminary collection of disease status/severity factors thought to impact neuropsychological presentation in SWS.
Physiatric findings in individuals with Sturge-Weber syndrome. Suskauer SJ, Trovato MK, Zabel TA, Comi AM. Am J Phys Med Rehabil. 2010 Apr;89(4):323-30.
Retrospective chart review of physiatric evaluation of 30 individuals, aged 4 mos to 55 yrs (median age, 2.4 yrs), with Sturge-Weber syndrome with brain involvement. Study summarized physiatric findings and recommendations in this cohort.
Behavioral and psychiatric features of Sturge-Weber syndrome. Turin E, Grados MA, Tierney E, Ferenc LM, Zabel A, Comi AM. J Nerv Ment Dis. 2010 Dec;198(12):905-13.
Studied a small group of outpatients (N = 16, age, 3-34 years) with Sturge-Weber syndrome seeking medical services to report their behavioral and psychiatric features.
Use of quantitative EEG in infants with port-wine birthmark to assess for Sturge-Weber brain involvement. Ewen JB, Kossoff EH, Crone NE, Lin DD, Lakshmanan BM, Ferenc LM, Comi AM. Clin Neurophysiol. 2009 Aug;120(8):1433-40.
Performed an observational study of qEEG results on eight infants with facial PW birthmark (four had SWS brain involvement). Recorded standard clinical EEGs and then derived a measure of asymmetry. Validated this threshold through a study of an additional nine infants with PW birthmark (five with SWS brain involvement). Quantitative EEG was able to distinguish between those infants with and those without brain involvement and should be further developed as a biomarker for the early screening of SWS brain involvement in at risk infants.
An infantile-onset, severe, yet sporadic seizure pattern is common in Sturge-Weber syndrome. Kossoff EH, Ferenc L, Comi AM. Epilepsia. 2009 Sep;50(9):2154-7.
The young age of onset and frequently intractable nature of seizures associated with Sturge-Weber syndrome (SWS) have been well-reported in large studies. However, many clinicians also anecdotally describe prolonged but sporadic seizure clusters. We analyzed data over a 5-year period from 77 children and adults with SWS in relation to sporadic seizure clusters. Sporadic seizure clusters were common and complicate the management of these patients.
Hemiparesis is a clinical correlate of general adaptive dysfunction in children and adolescents with Sturge-Weber syndrome. Reesman J, Gray R, Suskauer SJ, Ferenc LM, Kossoff EH, Lin DD, Turin E, Comi AM, Brice PJ, Zabel TA. J Child Neurol. 2009 Jun;24(6):701-8.
Study sought to identify neurologic correlates of adaptive functioning in individuals with Sturge-Weber syndrome. Hemiparesis identified on neurologic exam correlated with the presence if impaired general adaptive dysfunction suggesting that hemiparesis when noted on clinical exam should trigger neuropsychological evaluation to address more global functional needs.
Sturge-Weber syndrome: ear, nose, and throat issues and neurologic status. Irving ND, Lim JH, Cohen B, Ferenc LM, Comi AM. Pediatr Neurol. 2010 Oct;43(4):241-4.
This study determined what types of ENT issues most affect patients with Sturge-Weber syndrome and identified symptoms and issues that should be screened for and evaluated in order to optimize neurologic outcome.
Transcranial Doppler ultrasound in children with Sturge-Weber syndrome. Jordan LC, Wityk RJ, Dowling MM, DeJong MR, Comi AM. J Child Neurol. 2008 Feb; 23(2):137-43.
Department of Neurology, The Johns Hopkins University School of Medicine, USA.
This research found that transcranial doppler is a safe way to measure blood flow abnormalities in SWS suggesting that it may be useful for tracking response to treatment in a clinical trial or monitoring progression in SWS.
Transcranial Doppler ultrasound is a noninvasive vascular assessment technique proved useful in the management of pediatric disorders predisposed to stroke and may have similar utility for Sturge-Weber syndrome. Eight children with Sturge-Weber syndrome had velocities measured in the major cerebral arteries via the Stroke Prevention Trial in Sickle Cell Anemia methodology. Velocities and pulsatility indexes were compared between the unaffected and affected sides. All subjects had reduced velocity on the affected side; the mean middle cerebral artery percentage difference was 20% (95% CI, 15%-25%). Pulsatility index was increased on the affected side; mean middle cerebral artery pulsatility index percentage difference, 34% (95% CI, 15%-53%). Six subjects also had reduced posterior cerebral artery velocity on the affected side. Side-to-side differences in middle cerebral artery and posterior cerebral artery velocities correlated with severity of MRI asymmetry (Spearman rho = 0.88, P = .02). Decreased arterial flow velocity and increased pulsatility index in the middle cerebral artery and posterior cerebral artery suggests a high resistance pattern that may reflect venous stasis and may contribute to chronic hypoperfusion of brain tissue. Further study of Transcranial Doppler in children with Sturge-Weber syndrome is indicated.
Quantitative EEG asymmetry correlates with clinical severity in unilateral Sturge-Weber syndrome. Hatfield LA, Crone NE, Kossoff EH, Pyzik PL, Lin DDM, Kelley TM, Comi AM. Epilepsia. 2007 Jan;48(1):191-5.
Department of Neurology, Kennedy Krieger Institute, Baltimore, MD 21205, USA.
This novel research found that decreased power by quantitative EEG analysis on the affected brain side of patients with SWS correlated with the severity of neurologic involvement. These findings indicated that quantitative EEG was likely to be useful for the early diagnosis of SWS and for monitoring progression and treatment response in a clinical trial.
PURPOSE: Sturge-Weber syndrome (SWS) is a neurocutaneous disorder with vascular malformations of the skin, brain, and eye. SWS results in ischemic brain injury, seizures, and neurologic deficits. We hypothesized that a decrease in quantitative EEG (qEEG) power, on the affected side, correlates with clinical severity in subjects with SWS. METHODS: Fourteen subjects had 16-channel scalp EEG recordings. Data were analyzed using fast Fourier transform and calculation of power asymmetry. Blinded investigators assigned scores for clinical neurological status and qualitative assessment of MRI and EEG asymmetry. RESULTS: The majority of subjects demonstrated lower total power on the affected side, usually involving all four frequency bands (delta, theta, alpha, and beta). qEEG asymmetry correlated strongly with neurologic clinical severity scores and MRI asymmetry scores. qEEG data generally agreed with the MRI evidence of regional brain involvement. In MRI-qEEG comparisons that did not agree, decreased power on qEEG in a brain region not affected on MRI was more likely to occur in subjects with more severe neurologic deficits. CONCLUSIONS: qEEG provides an objective measure of EEG asymmetry that correlates with clinical status and brain asymmetry seen on MRI. These findings support the conclusion that qEEG reflects the degree and extent of brain involvement and dysfunction in SWS. qEEG may potentially be a useful tool for early diagnosis and monitoring of disease progression in SWS. qEEG may prove useful, in severely affected individuals with SWS, for determining regions of brain dysfunction.
Dynamic MR perfusion and proton MR spectroscopic imaging in Sturge-Weber syndrome: correlation with neurological symptoms. Lin DD, Barker PB, Hatfield LA, Comi AM. J Magn Reson Imaging. 2006 Aug; 24(2):274-81.
Division of Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. firstname.lastname@example.org
This work demonstrated that perfusion MR deficits correlate with the severity of neurologic impairment in SWS indicating that it will likely be useful for tracking response to treatment in a clinical trial and neurologic progression.
PURPOSE: To investigate physiological alterations in Sturge-Weber syndrome (SWS) using MR perfusion imaging (PWI) and proton spectroscopic imaging (MRSI), and their association with neurological status. MATERIALS AND METHODS: Six consecutive patients with a clinically established diagnosis of SWS underwent MRI using a 1.5 Tesla scanner. The protocol consisted of conventional anatomic scans, dynamic PWI, and multislice MRSI. A pediatric neurologist evaluated the neurological scores, and the imaging results were correlated with neurological scores using nonparametric correlation analysis. RESULTS: Two patients had classic neuroimaging findings of unilateral cerebral atrophy with corresponding leptomeningeal enhancement and hypoperfusion (prolonged mean transit time). Two patients had bilateral disease, and two had normal symmetric perfusion. Among clinical measures, the highest correlation was between hemiparesis index and hypoperfused tissue volume (Spearman's correlation coefficient, rho = 0.943, P < 0.05). There was also a trend of correlation, although not statistically significant (P = 0.06), between the hemiparesis score and the NAA/Cr ratio in the mid to posterior centrum semiovale, lateral gray matter (GM), and splenium. CONCLUSION: In SWS, PWI indicates cerebral hypoperfusion predominantly due to impaired venous drainage, with only the most severely affected regions in some patients also showing arterial perfusion deficiency. The extent and severity of the perfusion abnormality and neuronal loss/dysfunction reflect the severity of neurological symptoms and disability, and the highest correlation is found with the degree of hemiparesis. These parameters may be useful as quantitative measures of disease burden; however, further studies in larger number of patients (and with a more homogeneous age range) are required to confirm the preliminary findings reported here.
Quantitative atrophy analysis correlation with clinical severity in unilateral Sturge-Weber syndrome. Kelley TM, Hatfield LA, Lin DDM, Comi AM. J Child Neurol. 2005 Nov;20(11):867-70.
Department of Neurology, Johns Hopkins University, Baltimore, MD 21297-1000, USA.
This study validated the new SWS neuro score against measurements of brain atrophy indicating that the SWS neuro score should be useful for research and as an outcome measure for clinical trials.
Sturge-Weber syndrome is a neurocutaneous disorder with vascular malformations of the skin, brain, and eye. The objective of this study was to determine whether cortical atrophy in patients with Sturge-Weber syndrome correlates with clinical severity. Eighteen subjects (age 4 months-35 years) with unilateral Sturge-Weber syndrome received a neurologic examination and submitted previous magnetic resonance imaging (MRI) films. A blinded investigator assigned clinical severity scores based on seizures, hemiparesis, visual field cut, and cognitive impairments. Computer-aided analysis of MRIs produced laterality scores for cortical volume asymmetry. A significant relationship existed between clinical severity and laterality scores (Spearman's rho = -0.804; P < .001). Laterality scores also correlated well with hemiparesis subscores and weakly with cognitive impairment subscores (Kendall's tau b; P < .05). Using this simple, computer-aided analysis, cortical volume asymmetry correlated with clinical status. This method offers the advantages of relative simplicity, objectivity, and wide applicability to films from outside institutions, as would be encountered in clinical practice.
Early characteristics of Sturge-Weber syndrome shown by perfusion MR imaging and proton MR spectroscopic imaging. Lin DD, Barker PB, Kraut MA, Comi AM. AJNR Am J Neuroradiol. 2003 Oct;24(9):1912-5.
This research reported on the new MR perfusion imaging showing in SWS that the abnormal vasculature results in severely impaired venous drainage from the involved region resulting in arterial perfusion deficits in that region.
We report the case of a 9-month-old boy with Sturge-Weber syndrome and new onset of seizure. Perfusion MR imaging showed early changes compatible with impaired venous drainage in the affected hemisphere, whereas proton MR spectroscopic imaging revealed a focal parietal area of elevated choline without significant alteration of N-acetylaspartate levels. The perfusion and subtle metabolic abnormalities are comparable with the extent of the overlying leptomeningeal enhancement, illustrating the early pathophysiological manifestation of this disease.
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