Sturge-Weber syndrome is a neurocutaneous disorder characterized by port-wine stain birthmarks on the face and leptomeningeal angiomas in the brain. It is caused by a somatic mutation in the GNAQ gene and results in failed regression of embryonic blood vessels. Clinical manifestations include seizures, glaucoma, intellectual disability, and stroke-like episodes. Diagnosis involves MRI, CT, lumbar puncture and EEG. Management is multidisciplinary and focuses on seizure control, glaucoma treatment, and monitoring for neurological deterioration. Prognosis depends on factors like early seizure onset and extent of brain involvement.
3. Brief Introduction
Sturge-Weber syndrome (SWS), also called
Encephalotrigeminal angiomatosis, is a neurocutaneous
disorder characterised by capillary malformations in the
-Face (Port-wine birthmark; typically V1&V2
distributions of the trigeminal nerve
-Brain (Leptomeningeal Angiomas)
-Eyes (Glaucoma)
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4. Brief Introduction
It was named in Honour of British Physicians,
-Dr. William A. Sturge and
-Dr. Frederick P. Weber
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5. Epidemiology
-The incidence of Sturge-Weber syndrome is estimated to
be 1 in 20,000-50,000 live births.
-Affects males = females
-No race predilection.
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6. Etiology
Sturge-Weber syndrome is a sporadic developmental
disorder caused by somatic mosaic mutations in the GNAQ
gene which is located on the long arm of chromosome 9.
A single nucleotide variant (c.548G→A,p.Arg183GIn)
Hence, not a heritable disorder.
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7. Etiology
This mutation causes alterations in regulation of the
structure and function of blood vessels, innervation of the
blood vessels, and expression of extracellular matrix and
vasoactive molecules
Low flow in the leptomeningeal capillary malformation
results in a chronic hypoxic state leading to Cortical Atrophy
and Calcifications
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8. Pathophysiology
-SWS is caused by residual embryonal blood vessels and
their secondary effects on surrounding brain tissue.
- A vascular plexus develops around the cephalic portion of
the neural tube, under ectoderm destined to become
facial skin.
- Normally, this vascular plexus forms in the 6th week and
regresses around the 9th week of gestation
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9. Pathophysiology
-Failure of this normal regression results in residual
vascular tissue, which forms the angiomata of the
leptomeninges, face, and ipsilateral eye
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10. Classification
The Roach Scale is used for classification:
Type I - Facial and leptomeningeal angiomas(LA);
patient may have glaucoma
Type II - Facial angioma alone (no CNS involvement);
patient may have glaucoma
Type III - Isolated LA; usually no glaucoma
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11. Clinical Manifestations (Facial)
Port-wine birthmark:
-Present at birth
-Most common type of vascular malformation,
-Overall Incidence 20-50%
-Mostly Unilateral (can be bilateral)
-Ipsilateral to brain involvement
-Also occurs in Trunk,Mouth Mucosa
and Pharynx
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12. Clinical Manifestations(Ocular)
Glaucoma:
-Predominant ocular abnormality
-Presents as buphthalmos in the newborn
-Occurs on the Ipsilateral eye
-Affects approximately one-half of patients
-Risk of glaucoma is highest in the first decade
-Need for ophthalmology life long
evaluation
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13. Clinical Manifestations(Ocular)
-Conjunctival and Episcleral hemangiomas
-Diffuse choroidal hemangiomas
-Heterochromia of the irides
-Tortuous retinal vessels with occasional arteriovenous
communications
-Optic nerve damage - Resulting in myopia,
strabismus, and visual field defects
(Homonymous Hemianopia)
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14. Clinical Manifestations(CNS)
Siezures:
-Seizures are often the first symptom of SWS.
-Occur mostly 1st yr of life; rarely during 1st month of
life.
-Occur in 70-80% of all SWS & >90% in those with
Bilateral brain involvement
-They may occur in the setting of an acute illness
- Associated with the acute onset of hemiparesis
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15. Clinical Manifestations(CNS)
Siezures:
-Initially, typically focal,(Contralateral side)→ generalized
tonic-clonic
-Less commonly associated; Infantile spasms, myoclonic,
atonic seizures
-Response to antiseizure medication is variable and
unpredictable
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16. Clinical Manifestations(CNS)
Leptomeningeal vascular malformation :
-Occurs in 10- 20% of cases when a typical facial
lesion is present.
-Malformation occurs on the same side as the port
wine stain.
- The parietal and occipital areas are affected most
commonly, although any portion of the cerebrum can be
involved.
- LVM in SWS are not static lesions but rather undergo
angiogenic remodeling
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18. Clinical Manifestations (CNS)
Hemiparesis and stroke-like events
- Hemiparesis often develops acutely in conjunction
with the onset of seizures.
-The deficit occurs contralateral to the intracranial
lesion
-The paretic extremity usually does not grow at a
normal rate, resulting in hemiatrophy.
-Some affected children have progressive loss of
motor function or have a series of stroke-like events.
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19. Clinical Manifestations(CNS)
Intellectual disability
- Children with SWS typically develop normally for
several months after birth,→ developmental delay.
-Present in at least 50%
-The course of cognitive change in children with SWS
is highly variable(↑ ↓ in IQ over time)
- Cognitive impairment can be obvious soon after birth,
especially in infants with extensive brain involvement.
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20. Clinical Manifestations(CNS)
Behavioral problems
- The risk for behavioural problems is associated with
poorer cognitive function and the presence of epilepsy
- Autism spectrum disorder and social communication
difficulties are also associated with SWS.
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21. Clinical Manifestations(CNS)
Neuroendocrine problems
- 18-fold ↑sed risk of growth hormone deficiency in
SWS compared with the general population
-Growth hormone deficiency occurs without
neuroimaging evidence of pituitary or hypothalamic
abnormalities.
Central hypothyroidism has also been reported in
SWS
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24. Principles of Management
-Multidisciplinary Approach and Symptomatic
-Seizure Control : AEDs & Hemispherectomy
-Prevention of Stroke-like episodes
-Prophylactic treatment for headache
-Monitoring and treating of glaucoma (Drug/Surgery)
- Laser Photocoagulation for PWS
-Endocrine evaluation & treatment
-
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25. Poor Prognostic Factors
-Early seizure onset
-Extensive leptomeningeal angioma (LA)
-Medically refractive seizures
-Relapsing or permanent motor deficits
-Headaches or mild trauma associated with transient motor
deficits
-Evidence of progressive neurologic damage
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26. Poor Prognostic Factors
-Focal seizures with subsequent generalization
-Increasing seizure frequency and duration
-Increasing duration of postictal deficits
-Increasing focal or diffuse atrophy
-Progressive atrophy or calcifications
-Development of hemiparesis
-Deterioration in cognitive functioning (loss of intellectual
abilities)
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27. Recent Updates on SWS
– GNA11 & GNB2 Somatic mutations have been implicated are
related to SWS
– Retrospective studies suggest use of low dose Aspirin & Vit D
in treatment of SWS
– Prospective drug trials have supported use of Cannabidiol &
Sirolimus in treatment of SWS
– Presymptomatic treatment with low dose Aspirin & AEDs
Show promising results in delaying seizure onset in some
patients
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Typically affecting but not limited to ophthalmic n maxillary dis Refered to as Triad of STUGE WEBER.
Who decribed it in detail stuge decribed –cutaneous, ocular n neuronal features in 1869 n weber documented radiological findings in 1929
Gnaq regulats, functions& develp of BV. Whole genome sequencing from affected n unaffected skin of patients with SWS identified . in the GNAQ gene similar results from large cohorts as well as non syndromic patients with PWBirtmarks demonstated similar changes
D timing of the Somatic mutation affects the clinical phenotype. If mutation occurring at earlier stage may affect a greater variety of precursor cells and lead to SWS. Whilst those occurring at later may affect only precursors of vascular endothelial cells and lead to nonsyndromic port wine stains
SWS is referred to as complete when both CNS and facial angiomas are present, and incomplete when only the face or CNS is affected.
4type
Caz glaucoma can occur at any time in life
Many patients have visual field defects, typically a homonymous hemianopia. This is due to the presence of a LCVM affecting one or both occipital lobes and optic tracts.
Some patients have long intervals without seizures, even without medication, while others have frequent or prolonged seizures despite high doses of multiple medications. (
New blood vessels sprout of
CT of Pt with SWS SHOWING Unilateral calcification and underlying atrophy of the cerebral hemisphere
The mechanism for this deterioration is uncertain. Suspected to be a cumulative effect of repeated thrombotic events within the LCVM or chronic disturbance of blood flow and oxygen delivery to the involved tissues.
lower IQ at follow-up in one longitudinal study included baseline abnormalities (EEG), high seizure frequency, and early frontal lobe involvement on brain MRI
GH secreting cells are particulary sensitive to vascular insults & thus may have increased risk of damage in SWS
The preferred neuroimaging technique for the diagnosis of SWS is brain MRI as demonstrates the LVM. There is a general consensus among experts that a negative brain MRI with gadolinium at one year of age can reliably exclude the presence of a leptomeningeal lesion
Non contrast CT (A&B) with SWS, epilepsy, and severe intellectual disability. shows extensive, bilateral gyriform calcifications in a curvilinear pattern often called the "tram track" sign. FLAIR MRI (C, D) shows extensive atrophy of left frontal and parietal lobes. E &F Postcontrast MRI in transverse axial and coronal planes (G) shows leptomeningeal enhancement consistent with leptomeningeal capillary venous malformations (LCVMs) in both cerebral hemispheres. In addition, choroid enlargement is also noted (D, F, G) and correlates with the extent of the LCVMs.
neuronal injury.Limited observational data suggest that low-dose aspirin may reduce the frequency and severity of seizures and stroke-like events
It has being demonstrated that earlier onset seizures correlated with more residual neurologic deficits and worse focal cerebral atrophy and that in most cases the course stabilized after age 5 years
Disease progression and neurological deterioration may occur in SWS. Although the actual LA is typically a static anatomic lesion
For all children diagnosed with SWS, use of low-dose aspirin (3 to 5 mg/kg per day) beginning in infancy. There is increasing agreement among experienced clinicians that low dose aspirin may be beneficial, with the rationale that antithrombotic therapy may prevent the progression of impaired cerebral blood flow and hypoxic-ischemic
