**1. Introduction**

Parkinson's disease (PD) is the second most common neurodegenerative disease following Alzheimer's disease, characterized by bradykinesia, rigidity, resting tremor and postural instability [1]. The long-term use of anti-Parkinsonian drugs has been found to be associated with dyskinesia and

symptom fluctuation. Since the introduction of deep brain stimulation (DBS) in 1980s, DBS has been accepted as a preferred surgical treatment for PD [2]. Internal globus pallidus (GPi) and subthalamic nucleus (STN) are the main stimulation targets [3]. In particular, bilateral STN DBS is known to significantly improve not only primary motor symptoms, but also non-motor symptoms, such as sensory symptoms and sleep disturbances [4,5].

Traditionally, DBS surgery is performed under local anesthesia (LA) and conscious sedation to evaluate clinical benefit and side e ffects by localizing electrophysiological target using microelectrode recording (MER) and/or intraoperative test stimulation while the patient is awake [6–15]. STN DBS has several advantages when implemented under LA. The spike features of MER can be analyzed, and symptom relief or side e ffects by stimulation can be evaluated with intraoperative macrostimulation. In addition, by using electrophysiological targeting using MER, it is possible to compensate for errors from planning based on preoperative imaging, which is caused by brain shift due to cerebrospinal fluid (CSF) leakage after dura opening. However, MER under LA requires PD patients to withstand surgical procedure with approximately 18 h of antiparkinsonian medication discontinued. Most PD patients are old age and have severe multiple neuro-skeleto-muscular symptoms due to comorbidity, such as spinal stenosis and herniated intervertebral disc. Moreover, patients have to wear a frame on their head during the entire procedure and undergo surgery with the frame fixed to the operation table; thus, the patients may su ffer from intolerable pain and psychological sequelae. The risk of hemorrhage risk also increases if an unintended large motion occurs due to cough or tremor during surgery. Patient cooperation is one of the factors that may influence the outcome after surgery.

Because of these concerns, many authors have consistently tried STN DBS under GA and reported that the clinical outcome is not inferior compared to under LA. However, there have been no randomized trials comparing DBS surgery under LA and GA due to logistical concerns. Only class II evidence has been compared through retrospective data analysis [16]. Here, we aimed to review previously published literature on STN DBS under GA as an alternative to STN DBS under LA. The technique and clinical outcome using intraoperative imaging and MER in DBS under GA are thoroughly reviewed along with the introduction of single-center experience of our institution.

### **2. STN DBS Using Intraoperative Imaging or Microelectrode Recording Under GA**

The DBS surgical procedure can be divided into two stages: the intracranial implantation of DBS electrodes and the implantation of implantable pulse generator (IPG). In the case of IPG implantation, GA is generally preferred because tunneling is required subcutaneously. For intracranial electrode implantation, the STN DBS procedure under LA and GA are similar, but the specific details are di fferent. The main di fference between the STN DBS surgical procedure under LA and GA is the intraoperative verification method for the intended target acquisition, i.e., test stimulation or intraoperative imaging with or without MER. An accurate electrode location is a key factor to determine the postoperative prognosis after STN DBS surgery [17–20]. Image verification of the lead position is an important step, whether intra- or postoperatively [21]. For STN DBS under GA, some centers perform intraoperative verification using MER even under GA, and other centers use intraoperative imaging without MER. We reviewed each method of STN DBS under GA using intraoperative imaging or MER, respectively (Table 1).


**Table 1.** Summary data of published literature presenting clinical outcome effect of after subthalamic nucleus deep brain stimulation under general anesthesia in

### *2.1. Using Intraoperative Imaging*

With the development of the quality of magnetic resonance imaging (MRI) over the past decades, it has become feasible to identify the STN boundary can to easily implement DBS under GA using direct targeting using advanced imaging [36]. The combination of direct targeting based on MRI visualization of anatomical structures and intraoperative imaging used to confirm accurate lead placement enables surgeons to accurately identify STN targets. It may allow STN DBS procedure to be performed in an asleep state under general anesthesia (GA) without neurophysiological test [37–39].

Successful clinical results on the intraoperative imaging to verify the accuracy of STN lead position instead of electrophysiological structure mapping or stimulation tests during DBS surgery have been reported [23,29,31,37,40–44]. In recent studies on the advancement of intraoperative imaging, no significant clinical results were found when compared to awake DBS [16,30,37,45,46]. However, most of these studies are retrospective analyses with a small number of patients and significant heterogeneity in anesthesia and surgical techniques. In addition, most of the studies were conducted in highly specialized centers with considerable experience in intraoperative imaging. Although these results may not be generalized to all DBS centers for these reasons, current results of STN DBS under GA are promising.
