Medication Summary
Medical therapy in patients with Sturge-Weber syndrome (SWS) involves many agents, including beta-blockers, carbonic anhydrase inhibitors, and prostaglandin analogues, that can be used to lower the intraocular pressure (IOP). Medical therapy can be used as an initial treatment, especially in late-onset glaucoma, but surgical therapy is the initial therapy in early onset cases.
Aqueous suppressants are typically used for initial medical therapy. Prostaglandin analogues may not be as effective in these patients, because the episcleral venous pressure is often elevated by dilated, tortuous episcleral veins. Corticosteroids are used to reduce inflammation.
Anticonvulsants
Class Summary
These agents are used to terminate clinical and electrical seizure activity as rapidly as possible and prevent seizure recurrence.
Lorazepam (Ativan)
Lorazepam is a sedative hypnotic with a short onset of effects and a relatively long half-life.
By increasing the action of GABA, which is a major inhibitory neurotransmitter in the brain, lorazepam may depress all levels of the CNS, including the limbic system and reticular formation.
It is important to monitor the patient's blood pressure after administering a dose. Adjust the dosage as necessary.
Carbamazepine (Tegretol, Epitol, Carbatrol)
Carbamazepine is effective for the treatment of complex partial seizures. It appears to act by reducing polysynaptic responses and blocking posttetanic potentiation. The drug's major mechanism of action is reduction of sustained, high-frequency, repetitive neural firing.
Phenytoin (Dilantin, Phenytek)
The primary site of action for phenytoin (and other hydantoins) appears to be the motor cortex, where this agent may inhibit the spread of seizure activity. Phenytoin may reduce maximal activity of brainstem centers responsible for the tonic phase of grand mal seizures. Dosing should be individualized. If daily dosing cannot be divided equally, larger dose should be given before retiring. A phosphorylated formulation, fosphenytoin, is available for parenteral use and may be given intramuscularly or intravenously.
Diazepam (Diastat, Valium)
Diazepam is an extremely lipid-soluble agent that enters the brain very quickly in the first pass and often stops seizures in 1-2 minutes. It modulates the postsynaptic effects of GABA-A transmission, resulting in an increase in presynaptic inhibition. Diazepam appears to act on part of the limbic system, the thalamus, and the hypothalamus, to induce a calming effect. It has also been found to be an effective adjunct for the relief of skeletal muscle spasm caused by upper motor neuron disorders.
Diazepam rapidly distributes to other body fat stores. Twenty minutes after initial IV infusion, the serum concentration drops to 20% of Cmax. Individualize the dosage and increase cautiously to avoid adverse effects.
Oxcarbazepine (Trileptal, Oxtellar XR)
Oxcarbazepine's pharmacologic activity comes primarily from its 10-monohydroxy metabolite. Studies indicate that this drug may block voltage-sensitive sodium channels, inhibit repetitive neuronal firing, and impair synaptic impulse propagation. Oxcarbazepine's anticonvulsant effect may occur by affecting potassium conductance and high-voltage activated calcium channels. Drug pharmacokinetics are similar in older children (>8 y) and adults. Young children (< 8 y) have 30-40% increased clearance compared with older children and adults. Children under 2 years have not been studied in controlled clinical trials.
Clonazepam (Klonopin)
Clonazepam is a long-acting benzodiazepine that increases presynaptic GABA inhibition and reduces the monosynaptic and polysynaptic reflexes. It suppresses muscle contractions by facilitating inhibitory GABA neurotransmission and other inhibitory transmitters. Clonazepam has multiple indications, including suppression of myoclonic, akinetic, or petit mal seizure activity and focal or generalized dystonias (eg, tardive dystonia). It reaches peak plasma concentration at 2-4 hours after oral or rectal administration.
Lamotrigine (Lamictal)
This agent is a triazine derivative that is useful in the treatment of seizures and neuralgic pain. It inhibits the release of glutamate and also inhibits voltage-sensitive sodium channels, which stabilizes the neuronal membrane. Follow the manufacturer's recommendation for dose adjustments.
Levetiracetam (Keppra, Keppra XR)
Levetiracetam is used as add-on therapy for partial seizures. Its mechanism of action is unknown, but it has a favorable adverse effect profile, with no life-threatening toxicity reported.
Valproic acid (Stavzor, Depakene, Depacon)
Valproic acid is chemically unrelated to other drugs used to treat seizure disorders. Although its mechanism of action is unknown, its activity may be related to increased brain levels of gamma-aminobutyric acid (GABA) or enhanced GABA action. Valproic acid also may potentiate postsynaptic GABA responses, affect potassium channels, or have a direct membrane-stabilizing effect.
For conversion to monotherapy, concomitant antiepileptic drug (AED) dosage ordinarily can be reduced by approximately 25% every 2 weeks. This reduction may be started at the initiation of therapy or delayed by 1-2 weeks if there is concern that seizures are likely to occur with reduction. Monitor patients closely during this period for increased seizure frequency. As adjunctive therapy, divalproex sodium may be added to the patient's regimen at a dosage of 10-15 mg/kg/day. Dosage may be increased by 5-10 mg/kg/wk to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses of under 60 mg/kg/day.
Zonisamide (Zonegran)
Zonisamide is indicated for the adjunct treatment of partial seizures with or without secondary generalization. There is evidence that is effective in myoclonic and other generalized seizure types as well.
Topiramate (Topamax)
Topiramate is a sulfamate-substituted monosaccharide with a broad spectrum of antiepileptic activity; it may have state-dependent sodium channel–blocking action. The drug potentiates inhibitory activity of the neurotransmitter GABA and may block glutamate activity. It is not necessary to monitor topiramate's plasma concentrations to optimize therapy. On occasion, the addition to phenytoin may require adjustment of the phenytoin dose to achieve optimal clinical outcome.
Phenobarbital
Phenobarbital exhibits anticonvulsant activity in anesthetic doses and can be administered orally. If the intramuscular (IM) route is chosen, inject phenobarbital into a large muscle, such as the gluteus maximus, the vastus lateralis, or other areas where there is little risk of encountering a nerve trunk or major artery. Injection into or near peripheral nerves may result in permanent neurologic deficit. Restrict intravenous (IV) use to conditions in which other routes are not feasible, either because the patient is unconscious, as in cerebral hemorrhage, eclampsia, or status epilepticus, or because prompt action is imperative.
Gabapentin (Neurontin, Gralise)
This agent has properties in common with other anticonvulsants. However, its exact mechanism of action is unknown. Gabapentin is structurally related to GABA but does not interact with GABA receptors. Increases in the daily dose are best tolerated when done slowly.
Pregabalin (Lyrica)
Pregabalin is a structural derivative of GABA. Its mechanism of action is unknown. Pregabalin binds with high affinity to the alpha2-delta site (a calcium channel subunit). In vitro, it reduces the calcium-dependent release of several neurotransmitters, possibly by modulating calcium channel function. Pregabalin has been approved by the US Food and Drug Administration (FDA) for neuropathic pain associated with diabetic peripheral neuropathy or postherpetic neuralgia and as adjunctive therapy in partial-onset seizures.
Tiagabine (Gabitril)
Mechanism of action in antiseizure effect unknown. However, believed to be related to its ability to enhance activity of GABA, major inhibitory neurotransmitter in CNS. May block GABA uptake into presynaptic neurons, permitting more GABA to be available for receptor binding on surfaces of postsynaptic cells and possibly prevents propagation of neural impulses that contribute to seizures by GABA-ergic action. Dosing modification of concomitant AEDs not necessary unless clinically indicated.
Felbamate (Felbatol)
Felbamate is an oral antiepileptic agent with weak inhibitory effects on GABA- and benzodiazepine-receptor binding. It has little activity at the MK-801 receptor-binding site of the N-methyl-D-aspartate (NMDA) receptor-ionophore complex. However, it is an antagonist at the strychnine-insensitive glycine-recognition site of the NMDA receptor-ionophore complex. Felbamate is not indicated as a first-line antiepileptic treatment. It is recommended for use only in patients whose epilepsy is so severe that the benefits outweigh the risks of aplastic anemia or liver failure. Most adverse effects during adjunctive therapy resolve as the dosage of concomitant AEDs is decreased.
Lacosamide (Vimpat)
This agent selectively enhances the slow inactivation of voltage-gated sodium channels, resulting in the stabilization of hyperexcitable neuronal membranes and the inhibition of repetitive neuronal firing. Lacosamide is indicated for adjunctive therapy for partial-onset seizures.
Beta-Blockers, Nonselective
Class Summary
These agents lower IOP by decreasing the production of aqueous humor.
Levobunolol (AKBeta, Betagan)
This is a nonselective beta-adrenergic blocking agent that lowers IOP by reducing aqueous humor production
Antiglaucoma, Carbonic Anhydrase Inhibitors
Class Summary
These agents lower IOP by decreasing aqueous production.
Dorzolamide (Trusopt)
Dorzolamide inhibits carbonic anhydrase in the ciliary processes, which decreases aqueous humor formation.
Brinzolamide 1% (Azopt)
Brinzolamide inhibits carbonic anhydrase in the ciliary processes, which decreases aqueous humor formation.
Antiglaucoma, Prostaglandin Agonists
Class Summary
These agents lower IOP by increasing aqueous outflow through the uveoscleral pathway.
Latanoprost 0.005% (Xalatan)
Latanoprost may decrease IOP by increasing the outflow of aqueous humor.
Corticosteroids, Ophthalmic
Class Summary
These medications are used to treat ocular inflammation.
Prednisolone acetate 1% (Pred Forte, Pred Mild, Omnipred)
This agent inhibits the edema, fibrin deposition, capillary dilation, and phagocytic migration of the acute inflammatory response, as well as capillary proliferation. It causes the induction of phospholipase A2 inhibitory proteins.
Dexamethasone ophthalmic (Maxidex, Ozurdex)
Dexamethasone ophthalmic decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reducing capillary permeability.
Triamcinolone (Triesence)
Triamcinolone is used to treat inflammatory reactions that are responsive to steroids. It decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing capillary permeability.
Antineoplastic Agents
Class Summary
These agents inhibit cell growth and proliferation.
Fluorouracil (Efudex)
Fluorouracil interferes with deoxyribonucleic acid (DNA) synthesis by blocking the methylation of deoxyuridylic acid, inhibiting thymidylate synthetase and, subsequently, cell proliferation.
Mitomycin (Mitosol, Carac)
Mitomycin interferes with DNA synthesis by alkylation and by cross-linking the strands of DNA.
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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 |
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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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- Medication
- Follow-up
- Questions & Answers
- Media Gallery
- Tables
- References
