Neuromodulation in epilepsy: TMS-EEG, DBS, repetitive TMS, cortical electrical stimulation: open and

Introduction:
Epilepsy is a chronic disorder that is thought to be caused by an imbalance between excitation and inhibition in the brain. Consequently, stimulation of brain structures, which might influence cortical excitability, could be used for the treatment of epilepsy.
Neurostimulation is referred to a set of different procedures that aim at stimulating the brain or other nerve structures for either diagnostic or therapeutic purposes. Neurostimulation can be performed at the level of peripheral or cranial nerves (VNS, TNS), the cortex or subcortical (DBS) structures. Several studies have demonstrated the efficacy of neurostimulation as treatment in different epilepsy types. Approximately 35% of patients with epilepsy are not satisfactorily controlled by medical treatment, referred to as drug resistant epilepsy (DRE). Patients with DRE are very difficult to manage. They usually have major disabilities, have a social disadvantage and have a higher risk of death from accidental causes, suicide, status epilepticus or Sudden Unexpected Death in Epilepsy (SUDEP). Resective surgery is only considered as a treatment option when the seizure-onset zone is localized during presurgical evaluation that can be removed without causing unacceptable neurological or cognitive deficits. It is estimated that in one third of DRE patients, surgery cannot be performed either due to the proximity of seizure-onset zone to highly eloquent cortex, or because multiple foci, bilateral or generalized epilepsy. Under these circumstances, neurostimulation can be an alternative option for these patients. Here we will describe the current options neurostimulation options.
Cortical Stimulation:
Neurostimulation of the superficial cortex or deep brain structures is an expanding field in clinical neurophysiology and also in epilepsy. Neurostimulation (NS) has different methodologies, which varies according to its application and across the different centres. whereas, invasive electrical stimulation it is delivered by intracranial electrodes. Invasive neurostimulation has two methodologies, open and close loops. Most systems in use are open-loop, due to the complexities involved in reliably identify seizure related activity.
Open-loop method: stimulation is delivered according to set parameters, that can be modified while the stimulation is applied. Open-loop systems continuously deliver an A/C electrical current either high frequency (typically above 60 Hz), or at low frequency (usually lower than 10 Hz). High frequency is thought to deactivate neurons whereas low frequency stimulation induces a mixture of activation and inhibition. Also, magnetic stimulation can be delivered as single, double and repetitive pulses. Repetitive transcranial magnetic stimulation (rTMS) seems to be capable of altering cortical excitability by neuromodulation of the stimulated area. The overall conclusion from these studies is that rTMS a statistically significant seizure reduction that critically depends on various methodological parameters including the accessibility of the epileptogenic zone throughout TMS.
Deep Brain Stimulation:
Deep structures from the brain, such as, subcortical nuclei can be identified using neurophysiological techniques. Electrical stimulation of these structures has been used as the treatment of movement disorders, epilepsy or psychiatric conditions.
Subthalamic Nucleus (STN):
Stimulation of this nucleus has effectively been used in the treatment of Parkinson’s disease. It also seems to be beneficial in the management of epilepsy through activation of the Nigral Control of cortical excitability, which involves the superior colliculus, STN and thalamus
Thalamic Stimulation:
Different thalamic nuclei have been considered as possible targets. A large multicenter randomized, double-blind study (SANTE® Stimulation of the Anterior Nucleus of the Thalamus in Epilepsy) included 87 participants. It found that 40% of patients experienced a 50% or greater reduction in their baseline seizure frequency 13 months after implantation. Deep brain stimulation through the centromedian nucleus of the thalamus appears to be particularly effective in the treatment of frontal or bifrontal seizures, and for those with severe generalized epilepsies, including Lennox-Gastaut syndrome, as extensively reported in around 50 patients recruited for 15 years
Conclusions:
The mechanisms of action of neurostimulation remain unknown. It has been suggested that neurostimulation provokes a reversible functional lesion, inhibiting the triggering and/or propagation of epileptic activity from the area of stimulation. Indeed, electrical stimulation with single pulses provokes periods of suppression in cellular firing lasting for up to 1300 ms in 26% of neurons,<ref name=":9" /> suggesting that repetitive stimulation may be able to suppress cortical activity.

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