Tuberous sclerosis or Bourneville-Pringle disease is a hereditary autonomal dominant neurocutanous syndrome, although between 50-70% are de novo mutations, which appear in patients without a previous family history.
It may be caused by various mutations (DNA disorders), but the two most frequent are gene TSCI (9q34) (tuberous sclerosis type l), and gene TSC2 (16p13) (tuberous sclerosis type 2). It has a world-wide incidence of 1/10,000. The diagnostic criteria for tuberous sclerosis are those of the National Institutes of Health (NIH) consensus, 1998.
It is characterised by the presence of hamartomatous lesions in different organs, including in the brain. Epilepsy is the most common symptom, around 80% of patients with tuberous sclerosis have epilepsy. In spite of antiepileptic drugs, about two thirds of cases present drug-resistant epilepsy, which is with poor control of the seizures in spite of drugs.
The brain lesions found in patients with tuberous sclerosis are:
- Cortical tuberosities (Tubers).
- Subependymal nodules ( 90 %)
- Subependymal giant cell tumour (10%)
- White matter disorders.
The lesions responsible for the epilepsy in these patients are cortical tuberosities (tubers). Particularly frequent among epileptic seizures are infantile spasms in children under 1 year, whereas older children and adults usually have partial simple and/or complex seizures and less frequently generalised tonic-clonic, atonic, tonic, myoclonic or atypical absence seizures. The combination of 2 or more types of seizure is quite common.
Patients with TSC2 mutations are more susceptible to presenting a history of infantile spasms and untreatable epilepsy.
About 50% of patients with tuberous sclerosis present more or less cognitive affectation and altered behaviour. It is well documented that refractory epilepsy worsens pre-existing cognitive deficiency and altered in behaviour.
Patients who present inadequate control of epilepsy in spite of trying two or more antiepileptic drugs, vigabatrin, ketogenic diet, should be assessed early as possible candidates for epilepsy surgery.
The success of epilepsy surgery largely depends on the pre-surgical study and the time of progress of the epilepsy. The pre-surgical study is understood to be all the clinical examinations, electroencephalograms, radiological tests whether invasive or not, that provide all the information necessary to determine the location of the epileptogenic focus. Invasive tests should only be resorted to whenever there is a difference between the clinical signs, the video-electroencephalogram and imaging tests (resonance, SPECT, etc.).
About 63 % of patients subjected to resective surgery are seizure free (Engel class l), probably due to advances in the location of the epileptogenic focus now available.
Tests forming part of a basic pre-surgical study:
– EEG
– Thin-slice brain MRI
Tests forming part of an advanced pre-surgical study:
– Video-EEG
– PET
– SPECT (ictal and interictal)
– SISCOM (combination of MRI and SPECT)
– Magnetoencephalography
The nuclear medicine tests (PET, SPECT) are of enormous value whenever the patient presents a normal brain MRI (no tubers observed, 10% of patients) and drug-resistant epilepsy.
Tests forming part of an invasive pre-surgical study, and which are only performed when the advanced pre-surgical study leaves doubts about the location of the epileptogenic focus:
– Placement of grid and strip electrodes by craniotomy
– Placement of deep electrodes (SEEG)
What type of surgery is available to a patient with drug-resistant epilepsy and tuberous sclerosis?
There are 3 types of surgical treatment:
1- Resective surgery (Resection of the cortical tuberosity) In those cases where studies determine that the tubers are responsible for the epilepsy. In general, the epilepsy not only lies in the tuber, but also in the surrounding brain area, for this reason surgery should be guided by electrocorticography (placement of grids directly on thr brain to locate the epileptogenic focus).
The purpose of pre-operative tests is to determine which of the tubers is responsible for the epilepsy, and whether it is only due to one tuber or whether there are more causes of the episodes.
2- Placement of a vagal nerve stimulator (VNS)
This is merely palliative surgery, which is not performed with to completely cure the epilepsy, but only to reduce the number of seizures. About 70% of patients manage to reduce the number of seizures and any seizure presented by patients after surgery are generally less severe. Furthermore VNS is not only effective for epilepsy, but may also improve the cognitive deficiency of the patient as well as their frame of mind due to the effects the stimulation has on the brain.
It consists of the placement of an electrode around the left vagus nerve on a cervical level connected to a pulse generator on the subclavicular level.
This type of surgery is only indicated when resective surgery is not possible either because of the location or number of epileptogenic foci.
After surgery the device must be programmed to adjust the different parameters of the stimulator and enable better control of the seizure.
3- Corpus callosotomy
This is palliative surgery, just like vagus nerve stimulation (VNS), but more aggressive. Currently indicated in cases of severe refractory epilepsy, where resective surgery cannot be indicated, and where VNS has failed.
This consists of resection of the anterior two thirds of the corpus callosum, a brain structure that connects the two cerebral hemispheres. This technique is an attempt to prevent the seizure from spreading to all the brain by cutting seizure propagation pathways (corpus callosum).
