China Medical Information Herald September 27, 2012 Volume 27 Issue 18 Parkinson’s disease (PD) is a chronic degenerative disease of the central nervous system with symptoms such as resting tremor, rigidity, bradykinesia, and postural and balance disorders, most commonly seen in middle-aged and elderly people. Research shows that the incidence rate of people over 60 years old is 1%. With the improvement of the living standard of our people and the prolongation of life span per capita, as well as the arrival of the aging society in China, the basic research and clinical diagnosis and treatment of this disease have been paid more and more attention. Zhang Dongfeng, Zhengzhou People’s Hospital Brain Hospital Since February 2012, the China PD Deep Brain Electrical Stimulation Therapy Expert Group has held symposiums in Suzhou, Sanya and Xiamen City, solicited opinions from various parties, and repeatedly discussed and formulated the “China Parkinson’s Disease Deep Brain Electrical Stimulation Therapy Expert Consensus”, which is aimed at better standardizing the indications and processes of China’s Deep Brain Electrical Stimulation (DBS) therapy, and providing a set of standardized diagnostic and treatment procedures for clinicians. doctors with a standardized diagnostic and therapeutic framework. This article provides a detailed explanation of the current status of diagnosis and treatment of PD, evaluation and selection of DBS therapy, preoperative and postoperative management, and other key points. Current status of diagnosis and treatment of Parkinson’s disease To date, the etiology of PD is still unknown and there is no complete cure for the disease. levodopa and dopamine agonists can be used in the early stage of PD, but as the disease progresses to the middle and late stages, drug resistance and drug-specific complications will occur, and then DBS can be considered to improve the symptoms of dyskinesia and improve the quality of life of the patients. DBS surgery belongs to one of the neuromodulation therapy techniques, also known as brain pacemaker surgery, is a new technique gradually developed in the field of stereotactic functional neurosurgery in the past 20 years, which is a new therapeutic means of treating functional brain diseases by implanting tiny electrodes into the brain and connecting them to a neurostimulator, thus electrically stimulating specific nuclei in the brain. Compared with the previous stereotactic brain nuclei destruction surgery, DBS has the advantages of reversible, adjustable, non-destructive, less adverse reactions and fewer complications, so it has become the preferred method of PD surgical treatment and gradually replaced the destruction surgery. This therapy was first used in China in 1998 and has been used for more than ten years. At present, DBS treatment centers in China are mainly concentrated in Beijing, Shanghai, Xi’an and Guangzhou. According to statistics, as of the first half of 2012, a total of more than 3,800 patients have received DBS surgical treatment in China, and the number of hospitals carrying out the procedure has gradually grown to more than 70. At present, the diagnosis of PD still mainly relies on clinical manifestations, and there is still a lack of specific imaging or laboratory examination indicators. According to a study in the UK, only 76% of PD diagnoses are compatible with pathologic diagnoses, and even the most experienced physicians cannot make a completely accurate diagnosis while the patient is alive. The therapeutic efficacy of current DBS for primary PD has been demonstrated, but its role for PD syndromes is unclear. Therefore, it is necessary to clarify the diagnosis first in patients who are interested in DBS treatment. The British PD Association Brain Bank Clinical Diagnostic Criteria are the internationally used diagnostic criteria for PD. For patients with confirmed diagnosis of PD, the severity of the disease needs to be evaluated in order to select an appropriate treatment plan, which is generally assessed using the revised Hoehn-Yahr classification. Evaluation and selection of DBS therapies In the early stage of PD (Hoehn-Yahr grade 1 to 2), patients respond well to medication, and may be given levodopa combination or dopamine agonists to control symptoms. In addition, it is difficult to distinguish early PD from Parkinsonian superimposed syndromes such as multiple system atrophy and progressive supranuclear palsy, so it is not advisable to treat DBS at an early stage. Patients with end-stage PD (Hoehn-Yahr grade 5) are often combined with cognitive and psychiatric disorders, and at this time receiving DBS treatment can no longer comprehensively improve their quality of life, so it is also not recommended to receive DBS treatment. The traditional view is that PD is caused by degenerative changes in dopaminergic neurons in the substantia nigra. However, recent studies have found that PD is a neurodegenerative disease that involves multiple regions of the central nervous system. According to Braak’s hypothesis, PD lesions begin in the olfactory bulb, medulla oblongata, and pons; then progress to the substantia nigra and other deep nuclei in the midbrain and forebrain, leading to typical movement disorder symptoms such as tremor, rigidity, and decreased movement; and finally to the limbic system and neocortex. An increasing number of scholars in clinical work have found that patients with PD also suffer from many non-motor disorder symptoms. These symptoms are caused by disease involvement of non-dopaminergic neurons (e.g., cholinergic, adrenergic, 5-hydroxytryptaminergic, glutamatergic), including: (1) mental disorders: depression, anxiety, cognitive disorders, hallucinations, apathy, and sleep disorders; (2) autonomic dysfunctions: constipation, low blood pressure, hyperhidrosis, sexual dysfunction, dysuria, and salivation; (3) sensory disorders: numbness, pain, spasticity, restless leg syndrome, and olfactory disorders. (3) Sensory disorders: numbness, pain, spasticity, restless legs syndrome, and olfactory disorders. Currently, the common targets of DBS for Parkinson’s disease are thalamic nucleus (subthalamic nucleus, STN), globus pallidus internus (GPi) and ventrointermediate nucleus (Vim). Numerous studies have confirmed that electrical stimulation of these nuclei can effectively improve the symptoms of dyskinesia in patients.STN and GPi electrical stimulation can comprehensively improve the three major symptoms of PD: resting tremor, muscle rigidity, and reduced movement, while Vim electrical stimulation is the most effective in the treatment of tremor.STN and GPi electrical stimulation can also alleviate the movement fluctuation and levodopa-induced dyskinesia (LVD), and can also reduce the symptoms of PD. induced dyskinesia (LID), but the mechanisms of action are not the same for both. After STN-DBS, patients were able to reduce the dosage of anti-PD medication, thus reducing LID; whereas no reduction in dosage was seen after GPi-DBS, and its effect was direct.Postural instability gait diffi culty (PIGD), also known as midline symptoms, can occur in advanced stages of PD and can be relieved in the STN- DBS surgery, with short-term remission but poor long-term results. It is noteworthy that some of the non-motor dysfunction symptoms are alleviated after DBS, which may be due to the improvement of motor dysfunction symptoms or the reduction of anti-PD drug dose, and the improvement of non-motor dysfunction symptoms by DBS is still lack of evidence support. The effectiveness of different targets for the treatment of individual symptoms of PD is shown in Table 3, whereas the optimal target is inconclusive and needs to be selected based on the patient’s specific situation and the experience of each surgical center. In addition, the consensus specifically emphasizes the importance of patient selection. Before performing DBS, the diagnosis and indications for PD should be reconfirmed and the optimal timing of surgical treatment for DBS should be determined. Since PD is a progressive disease and DBS surgery is only a symptomatic treatment, premature surgery is not desirable, but blindly delaying the timing of surgery is equally unwise. Age and disease duration are important factors in patient selection for DBS surgery. Younger patients have a better chance of improving quality of life and dyskinesia symptoms, as well as fewer cognitive complications and slower deterioration of central axial symptoms; patients with a disease duration of 5 years or more, especially if the efficacy of medications has declined significantly, or if severe motor fluctuations or anisocoria are present, are the best time to consider DBS implantation. The levodopa shock test is an important predictor of DBS efficacy and should be completed preoperatively, with an improvement of ≥30% signaling a potentially better surgical outcome. Magnetic resonance imaging (MRI) or CT examination of the brain can show the presence of severe cerebral atrophy, cerebral infarction, etc., which can be used to determine the existence of contraindications to surgery and to assess the difficulty of surgery and target selection. For older patients or patients with longer disease duration, special attention should be paid to the presence of cognitive and psychiatric disorders; the ultimate goal of DBS surgery is to improve the patient’s quality of life, and patients with severe cognitive and psychiatric disorders will not benefit from the surgery even if their motor symptoms improve. It is important to note that DBS surgery is safe, but not risk-free, and some serious and permanent complications may occur, but the probability is low. Emphasis on preoperative and postoperative management Close collaboration and cooperation among neurologists, neurosurgeons, psychiatrists, and psychologists is important for the successful implementation of DBS therapy. Preoperative diagnosis of the patient’s condition, determination of whether the patient is suitable for surgery, whether there is a combination of cognitive and psychiatric disorders, assessment of the risk of surgery and the near- and long-term efficacy of the surgery, determination of the optimal surgical target (those who can accept and perform the surgery), the programmed control of the parameters of the DBS stimulation after the surgery, the adjustment of the anti-PD medication, psychotherapy, functional rehabilitation training, follow-up, etc., all of these require the participation of the functional neurosurgeon, psychiatrist, psychologist, and the neurosurgery department, psychiatry, and psychology, all of which require the participation and cooperation of functional neurosurgery, neurology, psychiatry, and psychiatrists. Usually, foreign PD patients receiving DBS therapy are recommended by neurologists, but most of the PD patients receiving DBS therapy in our country nowadays go directly to hospitals with DBS surgical capability, rather than being recommended by neurologists. Therefore, it is worth emphasizing that it is very necessary for any hospital that carries out DBS therapy to establish a DBS team consisting of physicians from functional neurosurgery, neurology, psychiatry, psychology, and rehabilitation to implement preoperative and postoperative management of patients in order to ensure that receiving DBS therapy achieves a satisfactory outcome. Studies have shown that most patients can reduce their anti-PD medications after surgery (although it is almost impossible to stop them completely), but to varying degrees. In addition, DBS stimulation parameters need to be adjusted after surgery through multiple follow-up visits (which takes about 3 to 6 months) until the stimulation parameters are optimized.DBS stimulation parameters are set appropriately and generally last about 5 years (the specifics of which are closely related to the patient’s treatment pattern). When the battery of the neurostimulator is about to run out, it needs to be replaced, but the electrodes and leads do not need to be replaced. It should be noted, however, that even when treated at the best centers, DBS electrodes may be implanted in an unsatisfactory position, and it may be necessary to implant the electrodes in a more satisfactory position by reoperation. Summary PD is a chronic degenerative disease of the central nervous system that progresses gradually and involves the whole brain, and a combination of medications, surgery, psychiatric-psychological treatment, and motor-function rehabilitation training is necessary to ensure maximum benefit to the patient. After DBS surgery, drugs are still a powerful weapon in the treatment of PD and should not be neglected. Clinicians should not only be skilled in the details of DBS treatment, but also inform every PD patient who intends to undergo DBS surgery.