Opportunities and Challenges of Facing the Coma of “Vegetative People” Correctly Craniocerebral trauma, cerebral hemorrhage, and ischemic-hypoxic brain injury can cause patients to enter a transient vegetative state (VS) or minimally conscious state (MCS), and some of them may even remain in this state forever without waking up. Since we often confuse the two states and refer to them collectively as “vegetative”, we put vegetative in quotation marks here. Both the general public and medical practitioners are pessimistic about the possibility of recovery when “vegetable” is mentioned. However, modern medical advances, especially the application of functional imaging and neuromodulation technologies, have made it possible for us to accurately assess and treat “vegetative patients”, but at the same time, we are also faced with many challenges. I. Challenges of Correct Assessment When we talk about “vegetative person”, is it a permanent vegetative state in our medicine? Is there no hope? Should we give up the supportive treatment of patients in vegetative state and let them die on their own? The New England Journal of Medicine, one of the world’s most authoritative journals of clinical medicine, has shown in a study of 54 patients with disorders of consciousness using functional neuroimaging techniques that 40% of the diagnoses of vegetative states are misdiagnoses, and that new methods of evaluation are needed to minimize the number of misdiagnoses. A portion of the patients diagnosed as “vegetative” may not be that serious and can be awake with aggressive treatment. According to Director Dong Yueqing, this prospective research on “vegetative” suggests that with the continuous development of science and technology, “vegetative” can be accurately evaluated through advanced testing methods (PET-CT and TMS-EEG). Evaluation. Currently, there are a lot of misjudgments and miscalculations of “vegetative state”, so the treatment can only be “making mistakes. Misjudging the condition of a “vegetative” person is difficult to reverse, and treatment is often abandoned or withdrawn; while misjudging the condition may delay treatment. Second, pay attention to the minimal consciousness state The real vegetable person, that is, what we call “permanent vegetative state”, the higher cortex function is completely impaired, this kind of patients in the treatment is really difficult, it is difficult to recover. Another part of the patient’s brain part of the normal function, between the various brain areas can not be fully connected, so their consciousness will be flickering wandering, not stable and reliable, this state is known as the “state of minimal consciousness”. When a person is in the minimally conscious state, he or she seems to be able to understand some things. For example, if a family member recounts familiar events from the past to a patient, the patient’s neural network responsible for language processing becomes significantly more active. What’s more, patients in a minimally conscious state are different from vegetative patients-they feel pain, only they have no way to show it, leading us to believe that they don’t feel pain. When they need painkillers, they should be provided with that need, but that is often not the reality. There are obvious differences between vegetative and minimally conscious states in terms of pathogenesis, pathophysiology, and treatment prognosis, and minimally conscious states are the subject of our choice of treatment and require our extra attention. Third, the opportunities and challenges of treatment The World Neuromodulation Society defines neuromodulation as a biomedical engineering technology that utilizes implantable or non-implantable technology, and adopts electrical stimulation or medication to change the activity of the central nervous system, peripheral nerves, or autonomic nervous system so as to improve the symptoms of the diseased population and enhance the quality of life. Neuromodulation is an emerging discipline, which emphasizes the regulation of nerves, and all the mechanisms of neuromodulation are not clear. Neuromodulation techniques currently applied to coma-induced awakening include deep brain stimulators (DBS), spinal cord stimulators (SCS), vagus nerve stimulators (VNS), and baclofen pumps. Although it is a worldwide challenge to restore patients’ consciousness, scholars at home and abroad have been exploring methods to promote patients’ recovery of consciousness as soon as possible. The following mainly introduces the progress of neuromodulation technology in this regard. First, Deep Brain Stimulation (DBS): also known as “brain pacemaker”, through the implanted electrodes in the brain to issue different frequencies of electrical stimulation to control the relevant nerve nuclei in the brain, to promote the patient to wake up. Since the 1980s, DBS has been used to promote the awakening of patients with minimal conscious state (MCS) and persistent vegetative state in clinical studies. The target points of stimulation are mostly chosen to be the reticular formation of the brainstem, the basal ganglia and the intralaminar nucleus of the thalamus (central nucleus of the thalamus – parafascicular nucleus complex), which are able to stimulate the brain in a diffuse manner, and to promote the recovery of consciousness of the patients. Second, spinal cord stimulation (SCS): As a kind of neuromodulation therapy, recently, the attention to spinal cord stimulation (SCS) for the treatment of disorders of consciousness is gradually warming up. Spinal cord stimulation (SCS) is performed by surgically placing stimulating electrodes in the cervical cord at the level of C2-C4 in the middle of the epidural area, and the electrical stimulation reaches the cerebral cortex through the upward reticular activating system and the subthalamic activating system. It has been reported that SCS modulates local cerebral blood flow, thereby triggering functional changes in neural circuits that are relevant to consciousness. The clearer view is that SCS modulates increased cerebral blood flow and is beneficial in ischemic encephalopathy. To date, published literature and data total 308 patients with PVS treated by SCS, with 51.6% showing clinical improvement. As the first hospital in China to develop this technique, our Coma Wake-Up-Rehabilitation Center has treated a total of about 92 patients in vegetative and minimally conscious states, with a wake-up rate of 62.5%. Third, Vagus Nerve Stimulation (VNS): Recently, French researchers applied vagus nerve stimulation to awaken a 35-year-old man who had been in a vegetative state for 15 years after a car accident. The results, published in the American Journal of Current Biology, challenged the widely held notion that a vegetative state lasting more than 12 months is irreversible. By stimulating the vagus nerve it may be possible to improve the patient’s current state of being. Vagus nerve stimulation (VNS), has been used in the treatment of epilepsy and depression. In addition the vagus nerve connects the brain to the rest of the body, and its role is important in many aspects of wakefulness, alertness and cognition. They chose to test the ability of the VNS to restore consciousness in a patient who had been in a vegetative state for more than 15 years without any signs of improvement, thus ruling out the patient’s ability to repair himself. After a month of vagus nerve stimulation, the patient’s attention, motor and brain activity improved significantly. The patient began to respond to simple commands. For example, he could track objects with his eyes and turn his head on demand. His mother said he was able to maintain some attention while the therapist read. After the stimulation, the researchers also observed the patient’s response to “threats”. For example, when the researcher’s head suddenly came close to the patient’s face, his eyes widened and he reacted with surprise. The researchers concluded that after the VNS treatment, the patient had moved from a vegetative state, which he had been in for many years, to a minimally conscious state. An EEG recorded major changes in the brain in motor, sensory, and cognitive areas, as well as an increase in functional brain connectivity, and a PET-CT scan showed an increase in metabolic activity in the cortex and subcortical areas of the brain. In conclusion, the treatment of “vegetative” coma in the past was indeed prohibitive, and only some conventional conservative treatments could be applied, but nowadays, with the development of brain science and neuromodulation technology, even patients with severe brain damage can produce changes in consciousness with the right intervention. Even if there is little hope, the plasticity of the brain and the ability of brain repair still exists. At the same time, we also need to recognize the limitations of the current treatment, the lack of understanding of the mechanism of consciousness generation, which limits the implementation of more effective treatment, so the current rate of awakening is not high. When facing the trusting gaze of patients’ families, who come from far away to seek treatment, my original intention of more than 10 years of coma treatment remains unchanged: “Wake up a patient, save a family”. Despite the difficulties, despite the bumpy road ahead, the window has been opened and the sun will always shine in! I would like to share my encouragement with all my colleagues who are engaged in the cause of coma awakening in China.