When Swedish neurosurgeon Professor Lars Leksell proposed the idea of the Gamma Knife in the 1950s, and even when the world’s first Gamma Knife prototype was born in Sweden in 1968, he would never have imagined that this medical device, which was almost a dream at the time, has become indispensable in the field of neurosurgery today; even the treatment of many diseases has been fundamentally changed as a result. However, the Gamma Knife has really entered the clinic until the 1990s. 1990 only 13 units of Gamma Knife in the world into use, the end of 1996 for 110 units. After the US FDA approval in 1997, the Gamma Knife has sprung up all over the world. Currently there are 249 Leksell Gamma Knives in operation worldwide. Mainland China was first introduced by Shanghai Huashan Hospital in 1993, and currently there are 17 units. And in 1996, Shenzhen, China’s Ovo also produced a rotary gamma knife with its own property rights, although not accepted in overseas markets, but the number is large in China. According to Leksell Sociaty statistics, as of December 2006, 202 of 249 gamma knife centers worldwide treated a total of 397,672 patients, with the main types of disease from multiple at least metastases (35.51%), meningiomas (12.46%), arteriovenous malformations (12.17%), auditory neuroma (9.26%), pituitary tumors ( 8.02%), glioma (6.48%) and trigeminal neuralgia (6.34%), accounting for a total of 90.25%. This does not include the number of cases treated with domestic gamma knife in mainland China, so even a conservative estimate of the number of cases treated with gamma knife is more than 550,000, and this is only the accumulation of the last decade or so. It is certain that the number of cases treated with gamma-knife will continue to rise; in contrast, the number of cases of open-heart surgery is declining. Gamma-knife treatment of AVM is the most satisfactory. Because of the high morbidity, the high risk of microsurgery and the difficulty of performing many of them, and the difficulty of curing interventional embolism; gamma-knife has the most advantages: less invasive, low complications and high cure rate, while the latency period for the onset of treatment is almost the only disadvantage. gamma-knife treatment of AVM in adolescents and adults was analyzed by Nicolato treatment, and the rates of complete occlusion were 85.5% and 87.6% at ≥3 years of follow-up, respectively. The time required for treatment to occlusion averaged 25.7 and 28.2 months, respectively, with permanent complication rates of 1.3% and 5.4%, respectively, and annual bleeding rates of 1.3% and 2.7%, respectively, during the treatment latency period. Sirin performed prospective staged gamma-knife treatment of giant AVMs (10.2 to 57.7 cm3 in volume), with good results; since giant AVMs either surgical or embolization treatment is unsatisfactory, Sirin’s report offers exciting prospects for the treatment of this type of recurrent disease. gamma-knife treatment of AVM not only reduces the bleeding rate, but also has positive implications for the improvement of cerebral hemodynamics, metabolism, and neurocognitive function. Auditory neuromas account for 8 to 11% of intracranial tumors. The incidence of facial palsy and hearing preservation after craniotomy are always unsatisfactory due to the surrounding structures. samii reported hearing preservation of 39%, facial nerve anatomy preservation of 73%, and mortality of 1.1%; meanwhile, the uneven surgical skills of neurosurgeons also confuse the choice of patients. In contrast, γ-knife treatment is becoming increasingly important in the management of auditory neuromas because it is relatively standardized and less subject to human influence. after a prospective comparative study of microsurgery and γ-knife treatment of untreated auditory neuromas less than 3 cm in diameter, Pollock concluded that γ-knife treatment is superior to open surgery for small to medium-sized auditory neuromas, unless longer-term follow-up shows an increased rate of tumor recurrence after γ-knife treatment. Hasegawa follow-up averaged 7.8 years, with 62% tumor shrinkage, 31% no change, and 7% enlargement; 93% tumor control at 5 years and 92% at 10 years; and 68% hearing preservation. The dose of gamma-knife treatment for auditory neuroma currently tends to be lower. Early reports tend to be higher, up to 13-15Gy, but recent studies have shown that the marginal dose of 12-13Gy can control tumor growth and complications will be significantly reduced. In the international γ-knife conference held in Seoul, Korea in 2006, many experts recommended the marginal dose of 12Gy. Pituitary tumors located in the central part of the brain, sensitive to gamma rays and easy residual surgery, suitable for gamma knife treatment. γ-knife treatment The primary goal is to control tumor growth, Wang Meihua et al. reported that non-functional adenoma had 97.6% growth control at 34.2 months follow-up, while Iwai reported 58.1% tumor shrinkage and 93% growth control after 5 years. Jezkova reported that GH adenoma treatment had stopped all tumor growth at 53.7 months follow-up, of which 62.3% had shrunk. The efficacy of gamma-knife treatment in improving endocrine abnormalities is positive, and its effect depends on the pre-treatment hormone level rather than tumor volume. gamma-knife treatment of pituitary tumors has low complications, and damage to the hypothalamus, pituitary stalk, and cranial nerves has been reported to be rare. Of greatest concern is the concern of causing hypopituitarism in the distant future. Foreign reports tend to have a high incidence of hypopituitarism, up to 26% to 28%. However, it must be pointed out that in most of these cases, often most patients (85%-100%) underwent transsphenoidal or craniotomy resection before γ-knife treatment, and none of these reports mentioned the pituitary function before γ-knife treatment, so it is reasonable to suspect that this part of hypopituitarism is not caused by γ-knife itself, but by tumor compression of the normal pituitary gland and surgical damage to the pituitary gland. In China, Liang Junchao et al. reported that γ-knife treatment of microadenoma not only did not cause hypopituitarism, but also improved the functional condition of pituitary gland. At present, MRI shows pituitary tumor very clearly, especially early enhancement can clearly show the boundary between pituitary tumor and normal pituitary gland; and the precision of γ-knife design and the characteristic of rapid decay of treatment dose outside the target point are sufficient to make the normal pituitary gland and pituitary stalk avoid the damage of large dose of gamma radiation, thus reducing the incidence of hypopituitary function; and the normal pituitary gland can tolerate gamma radiation dose up to 130Gy, the dose of gamma-knife treatment is not sufficient to cause hypopituitarism. The dose of gamma-knife treatment for pituitary tumors varies widely, with lower doses required for tumor growth control, mostly 10-14 Gy; however, the dose required for endocrine improvement is much higher, so the dose for functional adenomas is often as high as 25-35 Gy. Brain metastases are the ideal target for gamma-knife treatment because of the limited lesions and most of them are sensitive to radiation, ranking first for a single disease. Gamma knife can achieve excellent results in terms of local tumor control rate; however, because patients with brain metastases tend to have metastases from other parts of the body, gamma knife treatment is limited to some patients in terms of prolonging survival time. gamma knife treatment of as many brain metastases as possible (≥4) can effectively prolong patients’ meaningful survival time. There are more studies on factors affecting the outcome of γ-knife treatment, including the time from detection of primary lesions to intracranial metastases, extracranial metastases, Karnofsky score, age ≤70 years, and total volume of γ-knife treatment. The current treatment of metastases focuses on three approaches, namely craniotomy, whole brain radiotherapy and stereotactic radiosurgery. The current study designs comparing gamma-knife and surgery mostly lack reasonable control and randomization, so none of the results can be scientifically compared statistically, and it is still impossible to make conclusive recommendations on the choice of craniotomy and gamma-knife. However, whole brain radiotherapy is widely used to treat intracranial metastases, and considering the high incidence of long-term complications of whole brain radiotherapy, especially the incidence of cognitive dysfunction after 6 months, which is more than 30%, it is of concern whether γ-knife therapy can replace whole brain radiotherapy. Currently, many studies do not advocate prophylactic whole-brain radiotherapy for brain metastases, but rather delayed whole-brain radiotherapy for patients with so-called radiation-resistant metastases that fail γ-knife therapy, or whole-brain radiotherapy for multiple metastases that cannot be fully treated with gamma knife. In patients with satisfactory tumor control (i.e., more than 5 months after γ-knife surgery before recurrence requiring surgical resection), a moderate to severe inflammatory cell response was observed, whereas in patients with unsatisfactory control, this response was mild or absent; also, this response was present only in the area irradiated by the tumor and was not found in the area around and away from the irradiated area; immunohistochemical examination revealed significant CD68-positive macrophages and CD3-positive T-lymphocyte population; also, increasingly pronounced vascular damage over time was observed. As one of the most intense types of human pain experience, it is significant to explore the treatment of trigeminal neuralgia. Traditional microvascular decompression surgery (MVD) has achieved very high cure rates, and other surgical approaches have struggled to surpass it in terms of treatment outcomes; however, gamma-knife is increasingly recognized in the treatment of trigeminal neuralgia due to its low risk and nearly similar treatment outcomes. regis reported retrospective follow-up of 100 cases, 83% had complete pain relief and 71% of patients did not require continued pain medication. All patients had improved quality of life indicators. The complications of γ-knife treatment are mainly facial numbness and facial hyperalgesia, with an incidence of 6-23% and no reported deaths or severe disabilities; this is a huge advantage compared to the 0.8% mortality rate of MVD. Compared with MVD, the only disadvantage of γ-knife treatment seems to be that the pain is not relieved immediately after treatment, and the interval between treatment and pain relief varies among treatment groups, with an average of 4.3-9.6 months (0-36 months). the mechanism of GK treatment is still unclear. However, it is certain that γ-knife does not cause destruction of the conduction bundle of the trigeminal nerve at the therapeutic dose, because the motor, sensory and sympathetic functions of the trigeminal nerve are not affected after treatment. The possible mechanism is that the effect of γ-knife radiation on sensory nerves raises the pain threshold, which may explain why the pain is only somewhat relieved or even ineffective in some patients. Although reports on the treatment mechanism are still lacking, it seems that TN with microvascular compression is also more likely to achieve good results with γ-knife treatment. Currently, most of the reported treatments use dual-targeting, with marginal doses of 35-45 Gy and the highest central dose of 70-90 Gy; the treatment target also tends to be unified, namely the so-called nerve root zone (REZ) adjacent to the trigeminal nerve and the pontine brain; single-targeting treatment is poor and has a high recurrence rate. Craniotomy is preferred for meningioma treatment, but attempting GK for mildly symptomatic, high-risk meningiomas is not a rational choice, and the number of cases treated with Gamma Knife remains high due to the high morbidity. Long-term follow-up showed that 94% of tumor growth was controlled, including 33% shrinking in size and 64% remaining unchanged; symptoms improved by 44% and remained stable by 52%. Heppner reported that γ-knife treatment of low-grade glioma had satisfactory results; Rades et al. found that complementary plus fractionated radiotherapy or γ-knife treatment was superior to no treatment in terms of similar local control rates for postoperative residual neuroepithelial tumors. γ-knife is recommended as the first choice for glioma remnants. In addition, gamma knife is also a reasonable choice for diseases with poor surgical and interventional results such as dural arteriovenous fistula, jugular venous bullae, and hypothalamic malformation tumors, and satisfactory results have been reported, but the number of treated cases is not large because of the low incidence of these diseases themselves. There is no doubt that the gamma knife is playing an increasingly important role in the treatment of neurological diseases. In particular, with the launch of the new generation of Leksell Gamma Knife “Perfexion”, the Gamma Knife has further improved in terms of treatment scope, precision, standardization and humanization. However, there are still many problems in the field of gamma knife treatment, which leads to the domestic although the number of cases of gamma knife treatment, but still not fully recognized in the medical system, at least not the number of cases consistent with the status of treatment; to solve these problems is urgent. First of all, the clinical and basic research of gamma knife treatment should be further strengthened. It has been more than 10 years since the Gamma Knife entered the clinic and treated patients on a large scale, so long-term follow-up evaluation will become a focus of future research. Through long-term follow-up, it can clarify which diseases have satisfactory long-term results, so as to establish more reasonable and detailed indications for gamma knife treatment; at the same time, by recognizing the long-term complications of gamma knife treatment, it can provide guidance for the determination of the current treatment plan. For example, pituitary tumor treatment of long-term pituitary function impact, benign tumor treatment of malignant transformation, etc., not only troubled patients, but also troubled many clinicians, hindering the clinical more widely carried out gamma knife treatment. Long-term follow-up is more significant for diseases with longer survival time, such as meningioma, pituitary tumor, auditory neuroma and trigeminal neuralgia. As for malignant diseases such as metastases and gliomas, as well as comparing the advantages and disadvantages of Gamma Knife and other treatment modalities, multi-center and disciplinary cooperation should be advocated and strengthened, and the design of scientific and reasonable randomized controlled prospective clinical studies is also a direction of Gamma Knife research, which can provide the theoretical basis of evidence-based medicine for the clinical application of Gamma Knife, thus promoting Gamma Knife to become the mainstream treatment in the field of neurosurgery. As for basic research, in addition to cross-disciplinary cooperation with radiation oncology, independent research should be conducted to explore the mechanism of gamma knife treatment by combining the special characteristics of gamma rays. However, it must be pointed out that these studies not only need a certain clinical and scientific basis, but also must establish detailed patient files and properly keep them for follow-up, so the establishment of a follow-up network of gamma knife treatment cases must be raised to a new level of understanding. At the same time, gamma knife market access requires strong intervention by the administrative authorities. Undeniably, the current domestic gamma knife treatment field is uneven, some hospitals do not even have the foundation of neurosurgery, just with a machine, a few clinicians can set up the so-called gamma knife treatment center, which led to serious complications in some treatment cases, such as pituitary tumor treatment led to double blindness, hypothalamus extensive radiation necrosis, not only damage the health of patients, but also in the medical field of gamma knife treatment has caused a bad impact, causing concern for many doctors. Now many gamma knife are market-oriented investment, in order to recover costs often excessive pursuit of the number of doctors because of inexperience or driven by economic interests, often no principle to expand the gamma knife treatment indications, the formation of the so-called “come one, do one” “shoot a gun for a place “situation. This is not only inconsistent with the rigorous medical science, irresponsible to patients, but also affects the clinical promotion of Gamma Knife. In fact, Gamma Knife practitioners should first have a foundation in neurosurgery work, as well as training in radiation oncology; and Gamma Knife centers should preferably be established within general hospitals, so as to provide comprehensive treatment for patients and maximize the protection of patients’ interests. Therefore, the national health authorities should establish corresponding strict and practical rules on the admission of gamma knife and supervise the implementation. In addition, the current number of gamma knife practitioners and cases treated has been very large, so it is necessary to establish a special association or group under the Chinese Medical Association Neurosurgery Branch for management, and this work is currently underway. In addition, there is a need to further strengthen the standardization of gamma treatment. In fact, less human factors, treatment process standardization is one of the great advantages of gamma knife and surgery, so from the entry conditions of the gamma knife center, the collection and preservation of patient data to gamma knife treatment indications, positioning methods, data transmission, dose planning, important brain structures and cranial nerve dose limits, etc., should be standardized and specified as much as possible, so as to achieve the effective combination of treatment standardization and implementation of individualized treatment. We look forward to the national health authorities to organize, by the main domestic gamma knife treatment center is responsible for the research and preparation of a gamma knife treatment specification, will greatly change the current artificial confusion in the field of gamma knife treatment. Finally, the popularity of gamma knife treatment and publicity still need to be strengthened. For example, the proportion of trigeminal neuralgia treatment in foreign countries reached 6.34%, much higher than in China, because of the lack of awareness of the domestic doctors and patients of gamma knife treatment of the disease; at the same time, the excessive publicity of the failure of gamma knife treatment cases also troubled many doctors, to a certain extent, reducing the referral rate. Therefore, objective and scientific education and training is also necessary. With the development of clinical application and research of gamma knife, it would be the best result if it could be included in the training program for general practice clinicians. In conclusion, gamma knife as a minimally invasive, high-precision stereotactic radiosurgery, its therapeutic effect has been proven in clinical applications and has become an indispensable tool for neurosurgery. Although there are still some problems that need to be solved, the development of gamma knife will surely change day by day in the future and bring benefits to more patients.