Acute and Long-Term Effects of Subthalamic Nucleus Stimulation in Parkinson's Disease

Abstract

In animal models of Parkinson''s disease (PD), it is postulated that the excessive output from the subthalamic nucleus (STN) plays a critical role. Selective lesions or high frequency electrical stimulation of the STN can alleviate parkinsonian symptoms in MPTP-treated monkeys. We decided to carry out STN stimulation in patients suffering from severe akinetic forms of PD. After approval of the institutional ethical committee, we operated on a parkinsonian patient aged 51, suffering for 8 years from a strongly disabling akinetorigid form of PD, complicated by an on-off effect (Hœhn and Yahr stage 5 in the worst-off motor phase). Stereotactic surgery was done on one side under local anesthesia. The theoretical target was chosen according to stereotactic atlases, based on ventriculographic landmarks such as anterior and posterior commissures (AC and PC). The final position of the chronic electrodes was optimized using electrophysiological recording and stimulation along with clinical assessment and surface EMG of agonist and antagonist muscles of the examined limbs. A spontaneous increase in neuronal activity was recorded in an area located 2–4 mm under the level of the intercommissural plane, 10 mm from the midline, at middistance between AC and PC. Within the same place, a 130-Hz stimulation induced acute and reversible akinesia alleviation mainly on the contralateral limbs, comparable to that obtained with dopaminergic drugs. No dyskinesia, such as hemiballism, was induced by introduction of electrodes or by stimulation. Then a long-term quadripolar DBS Medtronic electrode was inserted in this area. Studies of the effects of chronic stimulation were extensively performed to determine the best spatiotemporal and electrical stimulation variables. Then, 3 weeks after implantation, the electrodes were connected to implantable programmable Medtronic Itrel II stimulators. A second patient has been operated since that time with excellent results so far. Effects of chronic unilateral and then bilateral stimulation are being tested. Mechanisms of stimulation which can induce similar effects to destruction of the same structure could be based on neuronal membrane blockade or on neural network jamming. Nevertheless, the interest of stimulation versus neural grafts must be discussed in patients with highly disabling forms of PD.