Deep brain stimulation in the treatment of epilepsy and Parkinson's disease

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Deep brain stimulation (DeepBrainStimulation'DBS) of the clinical application of nearly 30 years of history, it is the use of stereotactic t


Deep brain stimulation (DeepBrainStimulation'DBS) of the clinical application of nearly 30 years of history, it is the use of stereotactic technique, through deep brain stimulation electrodes embedded in, direct electrical stimulation applied in brain regions associated with disease, stimulator control and adjust the strength, wave width, frequency and other parameters of stimulation from outside the brain. Compared with other methods of nerve stimulation, DBS has the advantages of clear target, high selectivity, reversible, adjustable, no damage and so on. In recent years, with the development of MRI, CT and other more advanced target stereotactic equipment, more precise stimulating electrodes and stimulator, DBS treatment becomes more accurate and safe. It has become a potential tool for the treatment of neuropsychiatric disorders, especially in patients with advanced Parkinson's disease and refractory epilepsy.

Mechanism and effect of stimulation

Deep brain stimulation for PD mechanism is difficult to ascertain, generally because the electrode implantation, the first is the direct interference of the electrode (possibly temporary brain edema caused by minor damage effect) inhibited the electrophysiological activity of nuclei. It was found that the tremor was significantly inhibited when the electrode was implanted in the early stage of stimulation, but the tremor appeared after 3 to 5 days, which was confirmed by Caparros_lefebvre. In the future, due to the high frequency electrical stimulation, the local brain tissue excitability changes, the nerve conduction is suppressed, cut off the nerve conduction loop which causes the PD tremor, thus has the very good suppression PD symptom. However, it is not clear whether the stimulation is caused by the direct stimulation of nerve cells by current dispersion, or by other factors coupling effects. Cooper suggested that the relief of dyskinesia was due to the increase of central nervous system inhibition caused by deep brain stimulation. Recent studies have also found that the improvement of PD symptoms after high frequency stimulation of STN is related to the interaction of Glu, DA, SP and other neurotransmitters. However, the exact mechanism remains to be further studied.

It is generally believed that deep brain stimulation has the same therapeutic effect as that of the thalamus or the globus pallidus. But the study found that the former is more desirable than the latter, especially the globus pallidus or STN stimulation is more suitable for the elderly, critically ill patients, and patients with bilateral lesions of dopaminergic drug induced dyskinesia of patients, and will not cause serious complications. Benebiol reported 46 cases of DBS, in which the tremor disappeared in 62% patients and improved significantly in 88%. Benabid STN stimulation was performed on 2 cases of severe PD patients, 2 patients showed myotonia during stimulation and akinesia symptoms improved obviously, physical activity increased significantly, increased flexibility. After 8 months of follow-up, the symptoms of PD disappeared, and the phenomenon of "on / off" caused by dopamine drugs was completely improved.

The application of 1 DBS in the treatment of advanced Parkinson's disease (Parkinson 'S disease, PD)

The treatment of PD is mainly dependent on dopaminergic drugs, but the drug itself can also cause adverse effects of exercise and other sports, but also because of fluctuations in plasma concentrations of on - off effect. Especially in the late stage of PD, dopaminergic drugs on the control of movement disorders is getting worse, the patient's life and spirit are seriously affected, the quality of life greatly reduced. In 1993, the first PD patients received subthalamic nucleus (subthalamic, nucleus, STN) of the high frequency stimulation, the tremor, rigidity and sluggish symptoms have been alleviated, taking levodopa dose reduction of 60%. Since then, a large number of clinical trials have confirmed that high frequency electrical stimulation of STN can effectively relieve the symptoms of advanced PD. At present the most used single bilateral electric stimulation, the stimulation intensity began to weak, then increased slowly until it reaches the optimal strength, that is to say the strength does not cause slow, it will not cause apathy and hypophonia. A 5 year trial found that high frequency stimulation STN, tremors and rigidity improved up to 70% ~ 75%, exercise can not be achieved 50% improvement. Similar results were obtained in a recent clinical trial. In addition, a randomized clinical trial involving 156 patients reported that the patient's motor function was improved by a factor of 41% and a gain of about $23%, respectively, compared with the time before and after medication. The long-term curative effect of STN high frequency electrical stimulation was stable, and the improvement effect of exercise was still more than 40% after 2 to 4 years.

Although STN stimulation can significantly improve motor function in patients with advanced PD, and significantly reduce the doses of dopaminergic drugs (about 1 / 3 of the patients after 5 years still using low doses of dopaminergic drugs, the required dose reduction of 54%), become the gold standard for the surgical treatment of PD, but the STN high frequency stimulation there are many side effects. And have no effect on atypical Parkinson disease.

Application of 2.DBS in the treatment of intractable epilepsy

The pathogenesis of epilepsy in the world's population was about 0.5% ~ 1%, which is not the symptoms of 30% patients were anti epileptic drug control, refractory epilepsy, probability in temporal lobe epilepsy refractory epilepsy is as high as 60% ~ 70%. At present, for the treatment of refractory epilepsy is the main method by surgical resection of epileptic foci, but 40% of the patients with refractory epilepsy is more difficult to focus, not suitable for surgery, and surgery often will inevitably damage the normal brain function. Some patients with recurrent epilepsy after surgery. Therefore, intractable epilepsy has been a difficult problem in clinical treatment.

Since 1978, DBS for the treatment of epilepsy, have found that electrical stimulation of epileptic foci and structure is closely related to epilepsy, thalamus, caudate nucleus, such as can, Papez loop structure of the posterior hypothalamus and cerebellum. Inhibition of seizures. The efficacy of DBS was closely related to the site of stimulation, the type of epilepsy and the parameters of stimulation.

The preliminary results show that DBS stimulates the anterior thalamic nuclei, beginning can make the frequency of seizure reduction of 38% in the short term, after 1 years, 50% of the patients decreased more than 60%, especially on the bilateral median temporal lobe epilepsy treatment had the best effect.

Mexico a long including 9 patients (18 months to 7 years) clinical trials also found that in the absence of median hippocampal sclerosis in temporal lobe epilepsy patients, high-frequency stimulation of hippocampus could inhibit the seizure of more than 95%; in patients with hippocampal sclerosis, the inhibition rate was 50% ~ 70%, all patients were not progress. Also found no side effects. However, some researchers have found that electrical stimulation of the hippocampus has limited effect on the improvement of mesial temporal lobe epilepsy. In order to evaluate the efficacy and safety of DBS in the treatment of mesial temporal lobe epilepsy more comprehensively and scientifically, and compared with the surgical removal of the hippocampus, some large-scale clinical trials are in progress.

In 1976, Cooper et al., for the first time, was used for the treatment of epilepsy by DBS, and 50% of patients were found to have a seizure reduction of more than 67%. Subsequent long-term (17 years) studies have shown that stimulation of the cerebellum with 10~180 Hz electrical stimulation of the cerebellum in the epithelial layer, can make up to 85% of patients with symptoms. A recent 5 cases of long-term clinical trials found that patients with generalized tonic clonic seizure of an average reduction of 41% to stimulate epithelial layer for a period of 6 months in the cerebellum, tonic seizures decreased by 43%. The inhibitory effects of epilepsy still exist in 2 years until after cessation of stimulation, when generalized tonic clonic seizure than before stimulation by 24%. No other side effects or complications were found except in 1 patients. However, clinical trials have found that cerebellar DBS has limited efficacy in the treatment of epilepsy. The research continues.

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