Therapeutic and physiopathogenic contributions of Deep Brain stimulation in Parkinson's disease

Ablative functional neurosurgery constituted during the first half of the 20th century the main treatment of advanced forms of Parkinson's disease. The surgical procedure was spectacularly efficient on tremor, but sometimes complications were not totally regressive and even more severe when surgery was bilateral, this leading to neurocognitive deficits or to speech problems. This, associated to the efficiency of levodopa, was at the origin of the almost total disappearance of this type of surgery during the '60s until the eighties. The rebirth of functional neurosurgery, necessitated by the appearance of dyskinesias, was possible in most part because of the development of techniques with a lower morbidity, such as high frequency stimulation (HFS). This was initially applied to the thalamic ventral intermedius nucleus VIM, and the low morbidity of the method has been demonstrated by the possibility to operate a large number of patients bilaterally without complication. The demonstration that the pallidal target, which had been abandoned during the '50s because of its low efficiency on the triad of symptoms of Parkinson's disease, was selectively efficient on dyskinesias, led naturally to apply HFS to this target. In 1990, the demonstration in the field of fundamental research of the role of the subthalamic nucleus as a key element of regulation of movement, suggested to register this nucleus into the list of targets, despite the risk of hemiballism that this structure presents when it is lesioned by haemorrhage, because of the good tolerance of HFS as a surgical method. This target quickly showed its remarkable efficiency on all symptoms of Parkinson's disease. Because of the reduction of the doses of dopaminergic treatments which were allowed, this target had also the capacity to reduce, indirectly, the intensity of dyskinesias. If the efficiency of the method is nowadays demonstrated as well as the stability on the long term of its results, the mechanism is still mostly not understood Moreover the physiopathogenic hypothesis suggests the possibility of a neuroprotective effect of the stimulation, which still needs to be clearly established at the experimental level as well as at the level of clinical applications.