脳内埋め込み電極と体内埋設型刺激デバイスを用いた不随意運動の治療 Deep Brain Stimulation for Involuntary Movements

In an attempt to control hypokinetic and hyperkinetic movement disorders, deep brain stimulation (DBS) has been developed during the last two decades by several investigators. In 1987, Benabid and his colleagues suggested the usefulness of high-frequency stimulation of the ventral intermediate nucleus of the thalamus for treating drug-resistant tremors and avoiding the adverse effects of thalamotomy. Since then, DBS has been used as an alternative to functional neurosurgery for movement disorders, and more recently, it has been applied to the treatment of epilepsy, obsessive-compulsive disorders and cluster headache, in addition to other applications in experimental models. In regard to the treatment of movement disorders, recent clinical studies have demonstrated that DBS affords great benefits in terms of improvement of the activities of daily living in patients with Parkinsons disease (PD), essential tremor, dystonia and poststroke hyperkinetic movement disorders. We have treated patients with movement disorders by DBS of the thalamic nuclei ventralis oralis (Voa/Vop) et intermedius (Vim), globus pallidus internus (GPi), and subthalamic nucleus (STN). The site of permanent electrode placement was identified using magnetic resonance imaging and multiunit extracellular recording. The implantable pulse generator was internalized after postoperative test stimulation for one week. The stimulation parameters were modified by physicians at each follow-up visit on the basis of the findings on neurological examination, as well as the patients report concerning the activities of daily living. The advantages of DBS include reversibility and controllability of stimulation. In addition, DBS carries a smaller risk of side effects, particularly when employed bilaterally. Thalamic DBS is useful for controlling tremor that is unresponsive to medication. DBS of the STN and GPi improves the motor functions in PD patients, mainly during the off-period. Moreover, STN-DBS attenuates levodopa-induced dyskinesia through reducing the requirement of DOPA, whereas GPi-DBS directly attenuates DOPA-induced dyskinesia. In addition, GPi-DBS is very useful for controlling the symptoms of idiopatic generalized dystonia. According to reports, DBS is associated with few serious adverse effects associated with DBS. In general, the operative mortality is less than 1%. The incidences of hemorrhage are in the range of about 1-6%, and the incidences of device-related complications, such as infection or skin erosion, are in the range of 3-26%. DBS is clinically effective in well-selected patients and should be considered as a treatment option for patients with medically refractory movement disorders. Despite its clinical usefulness, the mechanism underlying the efficacy of DBS is still unclear. There is no proof currently that long-term DBS can reset neural networks or induce profound modifications of functional organization. Several researchers have proposed hypotheses concerning the mechanism underlying the efficacy of DBS, including 1) jamming of neural transmission, 2) direct inhibition of spike initiation at the level of the membrane that may be due to the activation of inhibitory terminals, 3) functional changes due to a decrease or increase in the amount of neurotransmitter released, and 4) retrograde activation of upstream neural structures. From the viewpoint of basic neuroscience, the development of DBS is intriguing. Investigation regarding the mechanism underlying the efficacy of DBS may provide clues for further clarification of various processes in the central nervous system.