tensor imaging is performed , and can be linked to epileptogenesis . 8 Furthermore , white matter abnormalities appear to be more evident in children with early onset and refractory epilepsy , with persistent seizures seeming to determine extensive connectivity alterations in brain areas crucial for language , social development and global cognitive functioning . 9
Management of tuberous sclerosis-related seizures Table 1 summarises treatment options for TSC-related seizures .
Anti-epileptic drug treatment The treatment of epilepsy associated with TSC still represents a great challenge for clinicians , due to the high rate of refractoriness , which is evident in up to 67 % of cases . 3 Early onset seizures should be promptly treated with vigabatrin , which has been shown to be able to stop infantile spasms in up to 95 – 99 % of cases . 10 Although its efficacy in focal seizures might be lower , treatment should not be delayed because it has been shown that a shorter gap from seizure onset and treatment initiation guarantees a better long-term outcome , both in terms of seizure refractoriness and neuropsychological evolution . 11 , 12 This kind of disease-specific efficacy of vigabatrin seems to be related both to its ability of increasing GABA concentrations in the synaptic cleft , as well as to a partial action on mTOR inhibition . 13 Vigabatrin can be associated with visual field constriction , but the benefit – risk ratio is strongly in favour of this treatment option . 14 Unfortunately , there are no other drugs showing such specificity ; therefore vigabatrin is the only anti-epileptic drug recommended . However , other drugs enhancing GABAergic transmission , such as topiramate and carbamazepine , could be used . 14 If polytherapy is necessary , anti-epileptic drugs showing synergism should be considered , and drugs with multiple mechanisms of action should be preferred in order to cover more seizure types . 14
Non-pharmacological options Surgery If the first two appropriately chosen anti-epileptic drugs fail to control seizures , a pre-surgical
Table 1
Treatment options for TSC-related seizures
Indications Advantages
Disadvantages / limitations
Anti-epileptic drugs |
|
|
|
Vigabatrin |
First line drug for early onset TSC associated seizures |
Rapid and high response of IS |
Possible ophthalmological toxicity |
Drugs enhancing GABAergic transmission |
Treatment for focal seizures starting after the first year of life |
Possible specific action in TSC due to the characteristic paucity of GABA at the synaptic level |
No real recommendations , no controlled studies showing the better efficacy of one drug over another |
Surgery |
TSC-associated epilepsy inadequately controlled after trials of two anti-epileptic drugs , and for well-defined lesions |
Data are limited but indicates that about 63 % of patients are seizurefree after surgery Success is increased by early intervention and accurate localisation of the epileptogenic region |
Patients with multiple bilateral epileptic foci might be not suitable for surgery |
Vagus nerve stimulation |
Refractory epilepsy in patients not suitable for epilepsy surgery |
Clinically significant response with a seizure frequency reduction higher than 50 % in about 70 % of treated patients |
Seizure freedom rare |
Ketogenic diet |
Refractory epilepsy in patients not suitable for epilepsy surgery |
Good clinical response Possible disease specific efficacy due to a partial action of mTOR inhibition |
High compliance needed |
mTOR inhibitors |
Refractory epilepsy in patients with TSC > two years |
Disease-specific efficacy Possible systemic action |
Long-term efficacy data still lacking |
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118 HHE 2018 | hospitalhealthcare . com |
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