Title : Pedunculopontine nucleus stimulation in intractable epilepsy: An innovative deep brain stimulation target
Abstract:
Intractable epilepsy (IE) continues to pose a medical challenge even today. Deep brain stimulation (DBS) is establishing as an effective adjunctive therapy in a selected category of patients with IE. Currently DBS of anterior thalamic nucleus in IE is FDA approved and newer targets are under exploration. Several studies have demonstrated the strong anti-epileptic influence of rapid eye movement (REM) sleep in humans; conversely, non-rapid eye movement (NREM) sleep that accounts for 75-80 percent of total night sleep is associated with increased proneness/susceptibility to epilepsy/seizure attacks. A reduction of REM sleep is a common feature reported in various forms of IE. Both, generalized as well as focal seizures have been reported to be suppressed during REM sleep. Several studies have reported reduction to total disappearance of even the severe EEG abnormalities (hypsarrhythmia EEG) in West syndrome (infantile spasms) during REM sleep. In autopsy examination of cases of West syndrome, the total number of neurons in pedunculopontine nucleus (PPN), a brain stem structure, and the number of acetylcholine neurons (AChN) in PPN in particular have been found to be reduced with relative preservation of catecholaminergic neurons and GABAergic interneurons suggesting a specific involvement of AChN in PPN in epileptogenesis. Stimulation of AChN in PPN has been observed to induce REM sleep. Therefore, in view of the strong anti-epileptic influence of REM sleep and the ability of PPN stimulation to induce/enhance REM sleep, it is postulated that PPN may be explored as a potential novel DBS target, which may be electrically stimulated (with programmable and manual modes) for enhancing the genesis of REM sleep throughout the night sleep time when the susceptibility to seizure generation and occurrence is marked because of NREM fraction. Thus, the postulated technique does hold promise as an effective anti-epileptic technique; albeit, warranting an insightful study of its prospects and success that may ensue from well designed preliminary trials on PPN stimulation.
Audience Take Away Notes:
- Deep brain stimulation (DBS) is an emerging and effective therapy for patients with intractable epilepsy that constitute about one-third of all patients with epilepsy
- The faculty dealing with patients with epilepsy will be able to use this knowledge not only in their research and teaching, but also in their clinical practice
- This technique will certainly provide the audience-clinicians an edge over their counterparts indulged in similar practice and/or teaching and research
- The novel target (PPN) will not only enhance the efficacy of treatment of the patients, but also broaden the spectrum of epileptic disorders for PPN-DBS
