Drug-resistant epilepsy: what are the alternatives?

Epilepsy is the third most common neurological disease today. Epilepsy affects 1% of the French population which represents 600,000 patients in France. Worldwide, we count 60 million, 50% of them are children (see Figure 1). Currently, the main treatments are drugs which stabilize 60% to 70% of epilepsies. Even if these drugs reduce the number of seizures, one third of epilepsies remain drug-resistant and uncontrolled. For patients whose epilepsy is not stabilized, the psychosocial consequences of the disease are numerous and they can lead to increased anxiety, difficulties in accessing schooling or employment… Seizures occurring during childhood can leave neuropsychological and neurodevelopmental aftereffects. On the medico-economic side, epilepsies are costly pathologies for the Health Insurance (it’s estimated that each drug-resistant patient costs between 3 200 and 6 000€ per year). Alcimed has analyzed for you the other existing or and emerging therapeutic ways to treat drug-resistant epilepsy.

First of all, what is epilepsy?

Epilepsy is a neurological disease that can take different forms, all characterized by a synchronized and abnormal excitation of a group of neurons in the cerebral cortex, which may secondarily spread to other areas. This anarchic excitation leads to seizures, focal or generalized, causing loss of consciousness, twitching and muscle contractions, as well as various neurological disorders (auditory, motor, visual, sensitive). Epilepsies also cause, beyond the seizures, cognitive disorders (memory, language, attention), mood disorders, behavioral disorders and sleep disorders.

Neurosurgery, a major beneficiary of technological advances

Surgery can be considered in certain cases, to remove or destroy the area that causes the seizures. Therefore, this area must be unique and well identified in order to be operated on. Moreover, it must be located at a distance from the highly functional areas, so as not to risk damaging them. There are several types of surgery:

• Resection surgery, which primarily treats mesiotemporal epilepsy. Surgery is seizure-free in 60 to 80% of cases. It is a 6-hour operation, under general anesthesia for young children and partial anesthesia for young adults. During the procedure, the surgeon is guided by a live recording of the patient’s brain activity (EEG).
• MRI-guided laser ablation (MRgLITT): ablation of the epileptogenic zone using an optical fiber, which is minimally invasive and reduces the length of hospitalization and after-effects.
• Thermo coagulation or thermo SEEG, allows thermo coagulation of epileptogenic foci, guided by stereoencephalography (use of SEEG electrodes already implanted on epileptogenic zones to perform thermo coagulation). The lesions of the epileptogenic zones are performed by radiofrequency.

Treatment of drug-resistant epilepsy: what is the place of palliative approaches?

Palliative approaches correspond to acts of neurostimulation, consisting in modulating neuronal excitability at distance to reduce the frequency and severity of seizures. These techniques were first tried 50 years ago to control epileptic seizures by electrical stimulation. These different approaches are more or less invasive:

• Some techniques are called non-invasive. This is the case with transcranial magnetic stimulation (TMS), which consists of a short series of magnetic impulses directed towards the brain to stimulate neurons and modify their excitability.
• Vagus nerve stimulation (VNS) is called semi-invasive. It is performed using a device (pacemaker type) implanted under the patient’s collarbone. The nerve is stimulated by intermittent current, which allows to inhibit the epilepsy and to reduce the medication doses. The technique has become more effective over the years, with 63% of patients who reduce their seizures by half.
• Finally, some approaches require an invasive intervention. Deep stimulation of the anterior nucleus of the thalamus (ANT-DBS) is an example. This is a safe, effective and well-tolerated third-line therapy. To stimulate these nuclei, an electrode is directly implanted in the patient’s thalamus by stereotaxis. The technique allows 70% of patients to reduce their number of seizures by 50%.

Surgery to treat drug-resistant epilepsy and palliative approaches are still not widespread. 40% of patients with drug-resistant partial epilepsy could benefit from this type of procedure in France, i.e. about 57,600 patients. However, only 500 patients are operated on each year, i.e. less than 1 for 100 potential candidates. There are still many fears related to surgical procedures on the brain although the latest technological advances in imaging and interventional techniques allow surgical operations to be more and more precise and less and less invasive. On the other hand, the study of epilepsy mechanisms can be extrapolated to other diseases affecting the conduction of nerve impulses, such as Parkinson’s disease and multiple sclerosis, for which applications are already being developed. Alcimed can help you in your projects related to these subjects. Don’t hesitate to contact our team !

Sources :

Épilepsie ⋅ Inserm, La science pour la santé

Filipescu C, Lagarde S, Lambert I, Pizzo F, Trébuchon A, McGonigal A, Scavarda D, Carron R, Bartolomei F. The effect of medial pulvinar stimulation on temporal lobe seizures. Epilepsia. 2019 Apr;60(4):e25-e30. doi: 10.1111/epi.14677. Epub 2019 Feb 14. PMID: 30767195.

Begley CE, Beghi E. The economic cost of epilepsy: a review of the literature. Epilepsia. 2002;43 Suppl 4:3-9. doi: 10.1046/j.1528-1157.43.s.4.2.x. PMID: 12059995.

Hect JL, Alattar AA, Harford EE, Reecher H, Fernandes DT, Esplin N, McDowell M, Abel TJ. Stereotactic laser interstitial thermal therapy for the treatment of pediatric drug-resistant epilepsy: indications, techniques, and safety. Childs Nerv Syst. 2022 May;38(5):961-970. doi: 10.1007/s00381-022-05491-x. Epub 2022 Mar 11. PMID: 35274185.

P. Kahane, S. Chabardès, A. Depaulis, Neurostimulation dans l’épilepsie, Pratique Neurologique – FMC, Volume 6, Issue 2, 2015.

Ryvlin P, Jehi LE. Neuromodulation for Refractory Epilepsy. Epilepsy Curr. 2021 Dec 15;22(1):11-17. doi: 10.1177/15357597211065587. PMID: 35233189; PMCID: PMC8832352.

La thermocoagulation multiple de foyers épileptogènes guidée par la SEEG (thermo-SEEG) – ScienceDirect

Who will use epilepsy surgery nomograms, and why? – The Lancet Neurology

About the author, 

Romain, Consultant in Alcimed’s Healthcare team in France