There are currently three surgical approaches for Parkinson’s disease, namely, nucleus pulposus destruction, deep brain electrical stimulation, stem cell transplantation and gene therapy.
1.Neuronucleus destruction
Nucleus nucleus destruction refers to the destruction of abnormal excitatory nuclei in the brain through stereotactic surgery to control Parkinson’s motor symptoms. The method of destruction is usually radiofrequency thermal coagulation destruction, gamma knife irradiation can not be intraoperative verification of the electrophysiological characteristics of the surgical site, surgical accuracy is reduced, easy to lead to hemiplegia, hemianopia and other complications, and slow onset of effect, is not recommended.
Pallidus bulb disruption can significantly improve tremor, muscle rigidity and bradykinesia in Parkinson’s disease, as well as drug-induced allodynia, and is the most commonly used disruption procedure for Parkinson’s disease. However, it is less effective for midline symptoms such as speech, cognitive function, autonomic function and gait disturbance in Parkinson’s disease patients, and slightly less effective than thalamic Vim nucleus disruption in controlling tremor. Although it has potential surgical risks, possible diminished long-term efficacy and the inability to operate bilaterally.
However, disruption is a destructive procedure and the long-term results are not satisfactory in some patients. Disruption is not suitable for bilateral brain surgery at the same time, and most patients have symptoms such as reduced speech, slow swallowing, drooling, and weakness after surgery; and the complications of bilateral thalamic surgery for cognitive impairment and balance disorders are as high as 40%. Even with staged disruption of contralateral asymmetric targets, there may be some impairment of intelligence, manifested by slowed reaction and poor near memory, and a significant proportion of patients have complications of urinary and fecal incontinence. Therefore, there are obvious shortcomings of disruption surgery, and bilateral disruption surgery is not easy to advocate, and this surgery is rarely performed abroad.
2.Deep brain electrical stimulation
Deep brain electrical stimulation uses stereotactic technology to implant stimulating electrodes into specific parts of the brain and suppress abnormal electrical activity of neurons through chronic high-frequency electrical stimulation, which can be adjusted by regulating the stimulating contacts of deep brain electrodes, output current, voltage, frequency and other factors to achieve the best treatment effect according to different clinical symptoms and changes of disease conditions.
Compared with destructive surgery, the advantages of deep brain electrical stimulation are reflected in.
(1) non-destructive effects on brain tissue.
(2) modifiability.
(3) Reversible side effects.
(4) Repeatable on/off for precise assessment of treatment effects.
(5) safe for bilateral surgery.
(6) preserves the possibility of receiving other new treatments in the future.
Ideally, deep brain electrical stimulation may achieve the following results.
(1) The motor function of the patient in the off phase is similar to the optimal state of the preoperative drug “on” phase in the electrical stimulation state;
(2) A reduction in the “off” phase.
(3) reduction of allodynia and motor fluctuations.
(4) Significant improvement in tremor, rigidity, and bradykinesia, which are the main motor symptoms of Parkinson’s disease.
(5) Bilateral symptoms can be controlled, especially midline symptoms such as rising, stepping, turning and rolling
(6) Speech disorders that can be improved during the “open” period can be improved after DBS.
(7) Mild postural instability can be improved, but severe balance disorders are difficult to improve.
The postoperative management of DBS is an important part of the treatment and sometimes determines whether the best outcome can be achieved. It includes
It includes:
(1) Post-operative program control: Because the micro-destructive effect of electrode implantation allows the patient to show significant improvement in motor symptoms even without stimulation 3-5 days after surgery, the first program control is usually started after 1 week. The procedure is usually performed in the “off” state of the drug, including the selection of the best electrode contact for stimulation, evaluation of the stimulation effect, evaluation of side effects, definition of the treatment window and setting of the stimulation parameters (during the “off” and “on” periods of the drug, respectively). “(2) Drug adjustment
(2) Drug adjustment: Usually performed when the stimulation is “on”, which is not exactly the same for different patients and different stimulation sites (GPi or STN). Patients with STN DBS can often reduce their levodopa dosage, and a few young patients can even stop it completely, with an average reduction of 50%, whereas patients with GPi DBS are rarely able to reduce their dosage. Levodopa drugs should be reduced gradually, and abrupt discontinuation should be avoided in patients on long-term, high-dose levodopa therapy because of the possibility of motor inability crisis. In addition, attention must be paid to non-motor symptoms such as apathy (lack of pleasure, lack of willpower) and even depression that occur during the drug reduction process.
(3) Post-operative DBS patient education: post-operative patient control needs to be repeated several times over the course of several months to a year in order to optimize stimulation and perfect synergistic treatment with medication.
The shortcomings of pacemaker therapy are the high cost and the fact that the pulse generator battery generally lasts only 3 to 6 years and the chest pulse generator needs to be replaced when the power is depleted. In addition, DBS device may produce infection, rejection or skin necrosis in some patients. Once the wound becomes red, swollen or broken, immediately return to the surgeon and remove the whole implantation system if necessary.
3.Gene therapy and stem cell transplantation
Although there are many clinically applied Parkinson’s disease drug treatments and surgical treatments, they are still symptom-specific treatments that do not stop the progression of the disease. We are counting on the research and development of Parkinson’s disease gene therapy and stem cell transplantation that can achieve neurological repair.
The so-called gene therapy is the use of specific methods to restore defective genes to normal. Parkinson’s disease is related to the functional defects of many genes and is a disease more suitable for gene therapy. The current gene therapy strategies for Parkinson’s disease mainly include.
1, neuroprotection: through the inhibition of apoptosis, nutrient protection cells, scavenging free radicals and other neuroprotection methods, reduce the loss and apoptosis of dopaminergic neurons in the brain of Parkinson’s disease patients, so that the proportion of nigrostriatal dopaminergic nerve cells is less than 80%, to avoid the emergence of clinical symptoms.
2.Neural repair: restoration and reconstruction of the substantia nigra and its surrounding microenvironment by enhancing the synthesis of dopamine in the brain and exogenous supplementation of replacement dopaminergic neurons.
3, functional reconstruction: direct injection of gene modifiers into the basal ganglia loops through stereotactic techniques to adjust the excitability status of input and output sites on the neural loops and reconstruct the functional balance of the loops.
As there are many transplantation genes available, the combination of different strategies of gene transplantation for Parkinson’s disease is the current direction of development, and the selection of vectors is working toward safety, effectiveness and high transfection rate, and the application of target cells is more inclined to clinical trials. If there is a breakthrough in gene therapy, perhaps Parkinson’s disease will become curable.
Stem cell transplantation should ensure a certain survival time of the graft and the safety of the graft itself. Prolonging the survival time of the graft and ensuring the normal secretion of neurotransmitters after survival are the problems that must be faced in transplantation for Parkinson’s disease.