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
evaluation should be promptly started to assess the
possibility of a surgical resection of the epileptic
focus. Although data are not homogeneous, seizure
freedom is achieved in a mean of 63% (range 25%
to 90%) of surgically treated patients, with better
results if the epileptogenic zone is accurately
localised and the surgery is performed promptly. 15
Vagus nerve stimulation
In patients not responding to anti-epileptic
treatment and for whom surgery is not an option,
vagus nerve stimulation should be considered.
Although data are limited, seizure freedom is quite
rare after vagus nerve stimulation implantation;
however, a clinically significant response with
a seizure frequency reduction higher than 50%
in about 70% of treated patients. 16
Ketogenic diet
In patients with refractory seizures who are not
candidates for surgery, a ketogenic diet should also
Table 1
Treatment options for TSC-related seizures
Indications Advantages Disadvantages/
limitations
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 seizure-
free 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
Anti-epileptic drugs
30 | Issue 90 | 2018 | hospitalpharmacyeurope.com