Approach Considerations
As soon as Sturge-Weber syndrome (SWS) is first suspected or documented, a complete ophthalmologic evaluation is essential to rule out glaucoma, since the infant's eye is damaged quickly by increased intraocular pressure (IOP).
In young patients, examination under anesthesia or deep sedation is necessary to confirm the diagnosis of glaucoma. Careful assessment in each eye of IOP, corneal diameter, cycloplegic refraction, axial length, and optic nerve cupping, as well as gonioscopic examination, is mandatory.
Cerebrospinal fluid (CSF) protein may be elevated, presumably secondary to microhemorrhage. Note that a major intracranial hemorrhage itself is rare in SWS, although microhemorrhage may be common.
Besides the clinical examination, the following have historically been the procedures of choice to establish the diagnosis (see Table 3, below) [1] :
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Angiography
-
CT scanning
-
MRI
-
MRI with gadolinium
-
Functional imaging - With SPECT or PET scanning
Table 3. Summary of Work-up Findings in Sturge-Weber Syndrome (Open Table in a new window)
Procedure |
Findings |
CSF analysis |
Elevated protein |
Skull radiography |
Tram-track calcifications |
Angiography |
Lack of superficial cortical veins Non-filling dural sinuses Abnormal, tortuous vessels |
CT scanning |
Calcifications, tram-track calcifications Cortical atrophy Abnormal draining veins Enlarged choroid plexus Blood-brain barrier breakdown (during seizures) Contrast enhancement |
MRI |
Gadolinium enhancement of leptomeningeal angiomas (LAs) Enlarged choroid plexus Sinovenous occlusion Cortical atrophy Accelerated myelination |
SPECT scanning |
Hyperperfusion, early Hypoperfusion, late |
PET scanning |
Hypometabolism |
Electroencephalography (EEG) |
Reduced background activity Polymorphic delta activity Epileptiform features |
Free thyroxine assay
A study by Siddique et al indicated that in patients with SWS who are taking anticonvulsants (which can cause abnormal results on thyroid function tests), a free thyroxine equilibrium dialysis assay is a more accurate means of diagnosing true hypothyroidism than is thyroid function testing. The investigators found that out of 5 children with SWS who were taking anticonvulsants and had been diagnosed with hypothyroidism using thyroid function testing, only 2 were revealed to have true hypothyroidism when tested with a free thyroxine equilibrium dialysis assay. [58]
Skull Radiography
Skull radiographs may show the classic double-lined gyriform pattern of calcifications paralleling cerebral convolutions referred to as “tram-track” (also called tramline, trolley-track, or railroad track) calcifications. These were considered pathognomonic for SWS in the era prior to modern neuroimaging, but they are often a late finding and may not be present initially.
Wilms et al reported tram-track calcifications in tuberous sclerosis with calcification located in extensive cortical tubers [59] ; Borns and Rancier reported these in childhood leukemia. [60]
Angiography
Angiography does not show the angioma but instead demonstrates a lack of superficial cortical veins, nonfilling of dural sinuses, and abnormal, tortuous veins that course toward the vein of Galen.
Fluorescein angiography has become a useful complementary examination in SWS. Angiography may reveal only an exaggerated background choroidal fluorescence early in the disease, widespread and irregular areas of hyperfluorescence secondary to diffuse leakage of dye from the surface of the tumor during the later stages of angiography, or even a diffuse, multiloculated pattern of fluorescein accumulation in the outer retina characteristic of polycystic degeneration and edema in more advanced disease.
Diffuse choroidal hemangioma may be overlooked easily on ophthalmoscopic examination because the color of the hemangioma resembles that of normal fundus, and the elevation may be minimal, especially in children.
Comparison of the red reflex in the eye being examined with that in the normal opposite eye can be helpful in confirming the diagnosis of a diffuse choroidal hemangioma; the normal eye may appear less orange.
CT Scanning
CT scans may show calcifications in infants and even in neonates, with SWS; other findings include the following:
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Brain atrophy
-
Ipsilateral choroid plexus enlargement
-
Abnormal draining veins
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Breakdown of the blood-brain barrier with seizures
In a study of CT scans in 14 children with SWS, conducted by Terdjman et al, cortical calcifications were present in 12 patients (see the image below), localized atrophy had occurred in 10 patients, and enlargement of the choroid plexus and abnormal veins were found in 7 patients each. [61]
MRI
Neuroimaging can confirm central nervous system (CNS) involvement. MRI has been reported to be superior to CT scanning in detecting the malformations affecting the CNS in SWS. However, the diagnosis is often obvious on plain skull radiography.
MRI allows recognition of abnormalities, including abnormal venous drainage and abnormal pial contrast enhancement, associated with the SWS angiomatous malformation that can confirm the diagnosis, even in very young children.
MRI also demonstrates cerebral volume reduction and ipsilateral choroid plexus enlargement. In addition, intravenous contrast can demonstrate the curvilinear posterior contrast enhancement of ocular choroidal angiomas. (See the images below.)
T1-weighted, axial magnetic resonance imaging (MRI) scans demonstrate left cerebral hemiatrophy associated with leptomeningeal angiomatosis. Image courtesy of Dr. Lamia Salah Elewa.
On the other hand, CT scanning is superior to MRI in detecting tram-track calcifications. However, these calcifications are usually not detectable before age 1 year and may not be seen for several years.
MRI with gadolinium enhancement
Although MRI does not show calcifications, gadolinium enhancement may show pial angioma; therefore, MRI may permit early diagnosis of SWS, even in newborns with a facial PWS. [62] Sugama et al reported that the most characteristic finding of SWS on MRI with gadolinium is enhancement of leptomeningeal angiomas (LAs). [63] LAs may be seen that did not appear on CT or angiographic images. MRI with gadolinium may also delineate the extent of the LA. Fischbein, however, reported that gadolinium enhancement may not be seen in every case. [64]
Hu et al reported that MR susceptibility-weighted imaging (SWI) may complement gadolinium-enhanced, T1-weighted MRI in characterizing abnormalities in SWS. [65]
MR spectroscopy and diffusion-weighted MRI
MR spectroscopy has shown increased choline but no reduction in the neuronal marker N- acetyl aspartate (NAA) in SWS, although in other reports, MR spectroscopy has shown decreased NAA. [66] Cakirer et al showed decreased NAA and increased choline in a patient with SWS, while the abnormal area also showed increased apparent diffusion coefficient (ADC) on diffusion-weighted MRI. [67, 68]
Regarding the MR spectroscopy findings in these studies, the decreased NAA was considered to represent neuronal loss, and the elevated choline was believed to demonstrate a lack of normal development.
BOLD MR venography
Mentzel et al reported that blood-oxygen-level-dependent (BOLD) MR venography may be sensitive in detecting early venous abnormalities in a case of SWS (earlier than conventional MRI sequences). [69]
MRI with DTI
Sivaswamy et al reported diffusion tensor imaging (DTI) abnormalities in the corticospinal tract of the affected hemisphere, which were seen before severe motor deficits developed. [70] In this study, the authors found lower fraction anisotropy (FA) values and higher ADC values of the cortical spinal tract in the affected hemisphere in 16 children with SWS (aged 1.5-12.3 y).
Interestingly, Moritani et al reported increased FA and decreased ADC in the subcortical white matter adjacent to the LAs in a term neonate aged 7 days with SWS. [71] As there are such varied findings on DTI and ADC, further studies are necessary to clarify the nature of DTI and ADC changes in SWS. It is likely that these changes are influenced by multiple factors, such as age and the stage of SWS.
Additional findings
Other MRI findings include accelerated myelination around the LA [72] ; a large choroid plexus, the size of which correlates with the extent of the LA [73] ; and progressive sinovenous occlusion on MR venography. Of note, Benedikt et al reported pial angiomatosis with adjacent cortical atrophy on MRI in 4 patients in whom unenhanced MRI or CT scan was normal or showed only nonspecific findings. [74]
Juhasz et al reported that cerebral hemisphere white matter volume ipsilateral to the angioma was an independent predictor of IQ, and that loss of such white matter volume may play a significant role in cognitive impairment in children with SWS. [75]
Bernal and Altman reported abnormal activation patterns in the occipital areas on functional MRI in patients with SWS. [76]
Lin et al reported perfusion MRI findings compatible with impaired venous drainage in an early case of SWS with new-onset seizures. [77]
SPECT and PET Scanning
SPECT scanning
This modality measures cerebral blood flow and demonstrates underperfusion in the area of the pial angioma; it may therefore detect a latent angioma not seen in other studies (see the image below). Using SPECT scanning, Reid et al demonstrated the presence of hypoperfusion before calcifications, anomalous drainage, or enhancement developed on either CT or MRI scans. [23] Griffiths et al showed that MRI and SPECT scanning together may reveal different areas of involvement. [78]
Namer et al demonstrated a steal phenomenon during seizures, causing ischemia in remote areas, with subtraction ictal SPECT co-registered to MRI (SISCOM). [79]
Pinton et al demonstrated that in infants with SWS, the cortex is hyperperfused during the first year of life before the first seizures occur. Classic hypoperfusion appears after 1 year of age, even in patients without epilepsy. [80]
Maria et al reported that enlargement of the choroid plexus correlates with abnormalities seen with SPECT scanning. [1]
PET scanning
In a pre-MRI study by PET scanning of children with SWS, Chugani et al demonstrated metabolic abnormalities in structurally affected hemispheres that extended beyond the anatomic abnormalities detected by CT scanning. [81] This result suggested that PET scanning might help to identify suitable candidates for hemispherectomy or focal cortical resection.
Transcranial Doppler Ultrasonography
In the diagnosis of diffuse choroidal hemangioma, A-scan and B-scan ultrasonography may be useful diagnostic aids. B-scan ultrasonography characteristically shows a solid, echogenic mass, whereas A-scan ultrasonography demonstrates high internal reflectivity. (See the ultrasonograms below.)
B-scan of a choroidal hemangioma showing medium to high internal reflectivity. This is a circumscribed choroidal hemangioma. The patient was not diagnosed with Sturge-Weber Syndrome. Image courtesy of Abdhish R Bhavsar, MD.
Jordan et al reported the use of transcranial Doppler ultrasonography in 8 children with SWS. Decreased arterial blood flow velocity and increased pulsatility were found in the middle and posterior cerebral arteries, suggesting high resistance. These results may reflect high venous stasis, potentially contributing to chronic hypoperfusion. [82]
Xenon Inhalation
Riela et al studied the xenon-133 (133 Xe) inhalation technique in 4 patients with SWS and demonstrated decreased regional perfusion in the area of the LA, with impaired vasomotor reactivity documented in 2 patients. [83] Decreased flow was prominent in 2 younger patients with normal neurologic status, suggesting that the blood flow abnormality may actually precede neurologic symptoms and may therefore cause or at least contribute to the deterioration.
Multiple Imaging Modalities
Determining the maximum extent of disease in patients with SWS may require a combination of structural and functional neuroimaging, since a mismatch may exist among neuroimaging modalities. Each modality may demonstrate abnormalities not detected by the other. This is especially important in the identification of the epileptogenic region when considering surgery for refractory seizures. A combination of modalities may also demonstrate a larger area of functional abnormality affected by SWS and potentially provide more information on prognosis.
Juhász et al studied 13 children with SWS using susceptibility-weighted images and DTI, in conjunction with PET scanning. SWI detected cortical abnormalities and deep transmedullary veins in the white matter adjacent to the hypometabolic regions. DTI detected abnormalities in the hypometabolic cortex and the adjacent white matter with collateral veins. [84]
Alkonyi et al reported 20 unilateral SWS patients with DTI and fluorodeoxyglucose (FDG)-PET scanning, measuring the diffusion parameters and FDG uptake in the thalami. Severe asymmetries of glucose metabolism and diffusion were strong predictors for low IQ. [85]
Electroencephalography
Electroencephalography (EEG) is used for the evaluation of seizures and for the localization of seizure activity in refractory seizures when epilepsy surgery is considered.
Brenner and Sharbrough reported unilateral reduction of background amplitude as the most consistent finding in the waking and sleep states, with activation procedures (hyperventilation and photic driving) decreased on the involved side. [86] EEG findings predated calcifications. Epileptiform activity was limited to the involved hemisphere.
In a study of children with SWS and epilepsy, Sassower et al reported marked voltage attenuation in the region of angioma in 13 of 14 patients; polymorphic delta activity (PDA) occurred in 12 of 14 patients. The PDA was unilateral in 6 of the dozen patients and correlated with the angiomatosis. None of the patients with unilateral PDA had mental retardation. In the 6 patients with bilateral PDA, 4 had mental retardation despite a unilateral angioma. Interictal spikes occurred in only 2 patients and were bilateral in 1 patient with unilateral disease. Seizures were recorded in 4 patients, and the ictal activity came from the periphery of the lesion. The seizures were refractory to treatment in 6 of 14 patients. [87]
Erba and Cavazzuti reported that late in the course of SWS, epileptiform activity might occur from the contralateral cortex. [40]
In a Canadian study, the EEG was normal in only 4%, background suppression occurred in 74% (unilateral in 64% and bilateral in 10%), and epileptiform discharges occurred in 22%.
Jansen et al reported asymmetry in beta activity in SWS, before and after diazepam administration in brain regions that structurally appeared intact. [88] The investigators suggested that diazepam-enhanced EEG may provide information on functional involvement and monitor progression of the disease.
Histologic Findings
The leptomeninges in SWS appear thickened and discolored by the LA, which fills the subarachnoid space, and abnormal venous structures are seen. Biopsies typically are not performed in SWS. However, pathologic specimens, such as those examined by Norman and Schoene, show calcium deposits in the cerebral vessel walls, in perivascular tissue, and, in rare cases, within neurons, as well as neuronal loss and gliosis. [17] These pathological abnormalities may occur at a distance from the actual vascular lesion.
Di Trapeni et al reported a mucopolysaccharide substance with calcium in the connective tissue of the vessels early on in SWS. This substance was found to increase in size and migrate outside the vessels. The investigators postulated that anoxia, necrosis, and variations in calcium concentrations act only as secondary factors. [89]
Hoffman et al have showed that aluminum was present within the calcium concretions, [90] and Simonati et al reported 4-layered microgyria below the angiomatosis. [91]
In skin biopsies of the PWS in patients with SWS, dilated, thin-walled vessels are seen in the superficial vascular plexus, but with no increase in the number of blood vessels.
In trabeculectomy specimens in patients with SWS, abnormal collagen depositions and abundant vessels in the intratrabecular spaces have been seen with morphologic abnormalities in the Schlemm canal. Hemangiomas in the trabecular meshwork are characteristic of SWS.
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A child with Sturge-Weber syndrome with bilateral facial port-wine stain.
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Cranial CT scan showing calcifications.
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MRI image in Sturge-Weber syndrome.
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Single-photon emission computed tomographic scan in Sturge-Weber syndrome.
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A child with Sturge-Weber syndrome that primarily affects the distribution of cranial nerve V2-3, with milder involvement of cranial nerve V1. Secondary glaucoma is evident. Ocular melanocytosis involving the sclera of both eyes is an associated finding. Image courtesy of Dr. Lamia Salah Elewa.
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Close-up view of the left eye, showing the Ahmed valve implanted in the inferotemporal quadrant after multiple failed filtration procedures induced severe superior conjunctival scarring. Intraocular pressure (IOP) was controlled. Image courtesy of Dr. Lamia Salah Elewa.
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T1-weighted, axial magnetic resonance imaging (MRI) scans demonstrate left cerebral hemiatrophy associated with leptomeningeal angiomatosis. Image courtesy of Dr. Lamia Salah Elewa.
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Ocular ultrasonogram of the posterior segment demonstrating the diffuse choroidal thickening seen in a diffuse choroidal hemangioma with "tomato-catsup fundus." Image courtesy of Dr. Lamia Salah Elewa.
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Choroidal hemangioma. Image courtesy of Thomas M. Aaberg, Jr, MD.
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Choroidal hemangioma. Image courtesy of Thomas M. Aaberg, Jr, MD.
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Circumscribed hemangioma. Image courtesy of F. Ryan Prall, MD.
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Circumscribed hemangioma. Image courtesy of F. Ryan Prall, MD.
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B-scan of a choroidal hemangioma showing medium to high internal reflectivity. This is a circumscribed choroidal hemangioma. The patient was not diagnosed with Sturge-Weber Syndrome. Image courtesy of Abdhish R Bhavsar, MD.
Tables
- Table 1. Clinical Manifestations of Sturge-Weber Syndrome
- Table 2. Developmental Morbidity Associated with Seizures in Adults with SWS
- Table 3. Summary of Work-up Findings in Sturge-Weber Syndrome
- Table 4. Seizure Control in Sturge-Weber Syndrome
- Table 5. Surgical Results of Hemispherectomy and Limited Resection from 3 Centers
Clinical Manifestation |
Incidence Rate |
Risk of SWS with facial PWS |
8% |
SWS without facial nevus |
13% |
Bilateral cerebral involvement |
15% |
Seizures |
72-93% |
Hemiparesis |
25-56% |
Hemianopia |
44% |
Headaches |
44-62% |
Developmental delay and mental retardation |
50-75% |
Glaucoma |
30-71% |
Choroidal hemangioma |
40% |
|
With Seizures (%) |
Without Seizures (%) |
Developmental delay |
45 |
0 |
Emotional/behavioral problems |
85 |
58 |
Need for special education |
71 |
0 |
Employability |
46 |
78 |
Procedure |
Findings |
CSF analysis |
Elevated protein |
Skull radiography |
Tram-track calcifications |
Angiography |
Lack of superficial cortical veins Non-filling dural sinuses Abnormal, tortuous vessels |
CT scanning |
Calcifications, tram-track calcifications Cortical atrophy Abnormal draining veins Enlarged choroid plexus Blood-brain barrier breakdown (during seizures) Contrast enhancement |
MRI |
Gadolinium enhancement of leptomeningeal angiomas (LAs) Enlarged choroid plexus Sinovenous occlusion Cortical atrophy Accelerated myelination |
SPECT scanning |
Hyperperfusion, early Hypoperfusion, late |
PET scanning |
Hypometabolism |
Electroencephalography (EEG) |
Reduced background activity Polymorphic delta activity Epileptiform features |
Study |
Complete |
Partial |
Refractory/No Control |
Gilly et al [95] |
NA* |
NA |
37% |
Sujanski and Conradi [42] (adults) |
27% |
49% |
24% |
50% |
39% |
11% |
|
Pascual-Castroviejo et al [39] |
47% |
12% |
28% |
Oakes [38] |
10% |
NA |
83% |
Sassower et al [87] |
NA |
NA |
43% |
Arzimanoglou and Aicardi [94] |
NA |
NA |
39% |
Erba and Cavazzuti [40] |
50% |
NA |
NA |
NA |
NA |
32% |
|
*NA = not available |
|||
Center |
Hemispherectomy |
Seizure Free |
Limited resection |
Seizure Free |
Improved |
Toronto |
12 |
11 |
11 |
8 |
2 |
Paris |
5 |
5 |
15 |
7 |
8 |
Boston |
9 |
8 |
6 |
3 |
0 |
Total |
26 |
24 |
32 |
18 |
10 |
24 of 26 patients with hemispherectomy - Seizure free 28 of 32 patients with limited resection - Seizure free or improved |
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- Overview
- Presentation
- DDx
- Workup
- Treatment
- Approach Considerations
- Pharmacologic Treatment of Seizures
- Pharmacologic Treatment of Glaucoma
- Headaches
- Strokelike Events
- Port-Wine Stain
- Surgical Treatment of Seizures
- Hemispherectomy
- Surgical Treatment of Diffuse Choroidal Hemangiomas
- Glaucoma Surgery
- Correction of Anisometropia and Strabismus
- Consultations
- Long-Term Monitoring
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