Benabid A L, Koudsie A, Benazzouz A, Vercueil L, Fraix V, Chabardes S, Lebas J F, Pollak P
Department of Neurosurgery, CHU A Michallon, Grenoble, France.
J Neurol. 2001 Sep;248 Suppl 3:III37-47. doi: 10.1007/pl00007825.
Chronic high frequency (130 Hz) stimulation (HFS) of the thalamic target Vim, first used in our group in 1987 as a treatment of tremor of various origins, has been used over the last ten years in 137 patients. Since 1993, this method has been extended to two other targets (subthalamic nucleus (STN): 137 patients and the medial pallidum (GPi): 12 patients), based on recent experimental data in rats and monkeys. STN appears to be a target of major interest, able to control the three cardinal symptoms and to allow the decrease or suppression of levodopa treatment, which then also suppresses levodopa induced dyskinesias. The stereotactic technique is based on the determination of the target using ventriculography, MRI and electrophysiology, with both microrecording of single neuron activity and microstimulation inducing therapeutic symptom suppression and side effects. Chronic electrodes are then placed bilaterally at the best physiologically defined location and then connected to implantable stimulators (either 2 Itrel II or the new double channel Kinetra), operated at 130-185 Hz, 60 ms pulse width, 2.5 to 3.5 volts. There was no operative mortality and permanent morbidity was observed in 3 patients. The mechanisms of action of HFS are not fully understood, but are definitely related to high frequency and are probably different depending on the target. Inhibition of cellular activity or of neural network functions could be induced, by jamming of a retroactive loop for tremor, or by shutdown of neurotransmitter release in STN. Mechanisms within an individual target are also probably different for tremor or for other symptom alleviation. All cardinal symptoms are alleviated from tremor to akinesia and rigidity. This strong improvement allows the decrease of the drug dosage to approximately 30% of the preoperative level, which suppresses the levodopa-induced dyskinesias. The off period dystonias are also suppressed as well as freezings and falls. The effects remain stable over more than 5 years and in the same period, the off stimulation-off medication UPDRS remains stable and does not increase at the usual rate The low rate of permanent complications, the minor side effects and their immediate reversibility, the possibility of bilateral implantation in one session and the long-term persistence of symptom relief are strong arguments which support chronic HFS of STN as the method of choice when a surgical procedure is indicated for the treatment of Parkinson's disease and even more when a bilateral procedure is necessary. Recent data show that STN stimulation could be useful in the treatment of dystonia as well as some forms of epilepsy. It is therefore possible that DBS in STN as well as in other targets could become a potent therapeutic tool in the near future for neurological disorders.
丘脑腹中间核(Vim)的慢性高频(130赫兹)刺激(HFS)于1987年在我们团队首次用于治疗各种原因引起的震颤,在过去十年中已应用于137例患者。自1993年以来,基于大鼠和猴子的最新实验数据,该方法已扩展至另外两个靶点(丘脑底核(STN):137例患者;内侧苍白球(GPi):12例患者)。STN似乎是一个主要的关注靶点,能够控制帕金森病的三大主要症状,并能减少或停用左旋多巴治疗,进而也能抑制左旋多巴诱发的异动症。立体定向技术基于脑室造影、磁共振成像(MRI)和电生理学来确定靶点,包括对单个神经元活动的微记录以及通过微刺激来诱发治疗性症状缓解和副作用。然后将慢性电极双侧放置在最佳生理定位处,再连接到植入式刺激器(2台Itrel II或新型双通道Kinetra),刺激参数为130 - 185赫兹、60毫秒脉冲宽度、2.5至3.5伏。无手术死亡病例,3例患者出现永久性并发症。HFS的作用机制尚未完全明确,但肯定与高频有关,且可能因靶点不同而有所差异。通过干扰震颤的反馈环路或阻断STN中神经递质的释放,可能会诱导细胞活动或神经网络功能的抑制。对于震颤或其他症状缓解,单个靶点内的机制可能也有所不同。从震颤到运动不能和强直,所有主要症状均得到缓解。这种显著改善使得药物剂量可降至术前水平的约30%,从而抑制左旋多巴诱发的异动症。关期肌张力障碍以及冻结现象和跌倒也得到了抑制。这些效果在超过5年的时间里保持稳定,同时,关刺激 - 关药物状态下的统一帕金森病评定量表(UPDRS)评分保持稳定,且未按通常速率增加。永久性并发症发生率低;副作用轻微且可立即逆转;能够在一次手术中进行双侧植入;症状缓解具有长期持续性,这些有力论据支持将STN慢性HFS作为帕金森病手术治疗的首选方法,尤其是在需要双侧手术时。最近的数据表明,STN刺激在治疗肌张力障碍以及某些类型的癫痫方面可能也有用。因此,STN以及其他靶点的脑深部电刺激(DBS)在不久的将来可能会成为治疗神经系统疾病的有效治疗工具。