HHE 2018 | Page 118

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
118 HHE 2018 | hospitalhealthcare . com