Abstract】Objective To investigate the efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in the treatment of dystonia. Methods Three patients with dystonia, two with unilateral subthalamic nucleus electrical stimulation and one with bilateral subthalamic nucleus electrical stimulation, were scored using the Burke Fahn-Marsden dystonia rating scale (BFMDRS) preoperatively and 3-22 months postoperatively. Results All three patients showed varying degrees of improvement in symptoms after start-up, with 97% improvement in case 1 at 22 months of follow-up; 63% improvement in case 2 at 3 months of follow-up; and 37% improvement in case 3 at 3 months of follow-up. No surgery-related complications occurred in all patients. Conclusion STN is an effective target for the treatment of dystonia and may provide significant, long-term improvement in dystonia symptoms. Dystonia is a movement disorder syndrome characterized by abnormal movements and postures caused by uncoordinated or excessive contraction of the active and antagonistic muscles, with involuntary and persistent characteristics. It can be classified as primary or secondary by etiology, limited, segmental, eccentric and generalized by site of occurrence, and pediatric, juvenile and adult by age of onset. From June 2012 to April 2014, three patients with dystonia were treated with deep brain stimulation (DBS) in the subthalamic nucleus (STN) and achieved good results, which are reported below. I. Clinical data 1. Case data: Case 1 female, 49 years old. She was admitted to the hospital in June 2012 due to “involuntary movement of the right upper limb and head with difficulty in head raising for more than 3 years”. 3 years ago, she developed involuntary swinging of the right upper limb, involuntary head shaking and difficulty in head raising without any obvious cause, accompanied by poor speech fluency and occasional choking; the swinging amplitude of the right upper limb was large and mostly higher than the head. The symptoms of involuntary movement and difficulty in raising the head can be partially relieved when the patient holds the head from behind the occiput with the right upper limb, but they cannot last. The symptoms are not obvious when lying or sitting, but worsen when standing, walking and nervousness, and it is difficult to take care of oneself. The symptoms were partially relieved by taking Antan, and the dosage was gradually increased to 10 tablets/day, which was discontinued due to obvious side effects. He had no previous history of obstructed labor, hypoxia, encephalitis or head trauma, etc. The DYT1 gene (dysfunctional tapetum) test was negative. 2010.5.20 cranial MRI showed atrophy of the cerebellar earthworms (Figure 1). There were no significant abnormalities in other ancillary examinations. Diagnosis: primary focal dystonia (right upper limb and head and neck). Case 2 male, 51 years old. He was admitted to the hospital in 2014.3 with “50 years of walking difficulty in the right leg, aggravated by stiffness of the limbs and difficulty in movement for 7 years”. at the age of 1 year, his family noticed that he could not land on the right heel when walking and had difficulty in walking. since 2007, he had swaying of both upper limbs with no obvious cause and progressive aggravation, accompanied by difficulty in walking. These symptoms disappeared during sleep and worsened during stress. He was taking alprazolam 2 tablets/time, 3 times/day, and benadryl 1 tablet/time, 3 times/day, and each dose only partially improved the symptoms for about 2-3 hours. No history of asphyxia or hypoxia at birth could be determined. No DYTI gene test was performed. 2014.3.29 Head MRI showed: multiple lacunar cerebral infarction. No significant abnormalities in other ancillary examinations. Physical examination: no obvious abnormalities in cognition, lack of fluency in speech, difficulty in walking, generalized writhing when walking, obvious abnormalities in posture and gait: inversion of the right foot with plantar curvature and inability to land on the heel, dragging of the left foot; the left upper limb was slightly against the trunk, the right upper limb was abducted, the head was skewed to the left side, slow movement of the left hand, muscle tone: grade 0 of the right upper limb, II+ of the remaining limbs. Diagnosis: primary generalized dystonia. Case 3 female, 65 years old. She was admitted to the hospital in 2014.3 with “difficulty in movement and stiffness of the left hand and left upper limb for more than 6 years.” In 2008, she developed numbness of the left little finger and ring finger without any obvious cause, and then developed inflexible movement of the left hand, which gradually developed to the whole left upper limb. 2 years ago, her symptoms developed into inability to extend the left hand, inability to straighten the left elbow in flexion, and inability to lift the left hand over the shoulder. Two years ago, the symptoms developed into inability to extend the left arm, to straighten the left elbow flexion and to raise the left arm over the shoulder. He had improved with clonazepam, but the efficacy gradually deteriorated. The treatment was not effective with Antan, Methocarbamol, Amantadine and Benadryl. He was injured by a fan blade on his right side in 1990. On February 17, 2012, cranial MRI showed cortical brain atrophy in the right parietal area (near the central sulcus) (Figure 2). There was no significant abnormality in other auxiliary examinations. Physical examination: high muscle tone of the left upper limb: grade 4 (stiffness) of the left hand, grade 3 muscle tone of the left elbow and shoulder joint, inability to straighten the left elbow, and inability to raise the left hand over the shoulder. Diagnosis: secondary focal dystonia (left upper limb), brain atrophy after right parietal brain contusion. 2. surgical approach: case 1 patient underwent left STN-DBS, case 2 patient underwent bilateral STN-DBS, and case 3 patient underwent right STN-DBS. all 3 patients were fitted with Leksell-G head frame (Elekta, Sweden) under local anesthesia, and then underwent 3.0T MRI (Siemens Trio) thin-layer localization scan (layer thickness 2mm, T2). The STN is a visible target under MRI, and the level where the STN is well displayed is selected for measurement and its coordinate value is calculated. The STN coordinates were x=11.5 mm, y=- 2 mm, z= 5 mm in patient 1, x=12 mm, y=- 3 mm, z= 6 mm in patient 2, and x=11 mm, y=- 2.5 mm, z= 5 mm in patient 3. After local anesthesia, a horseshoe-shaped flap was made 11-300 px above the interbrow and 3.5-4 cm paralleling the midline to the frontal side. After cranial drilling, microelectrodes (Medtronic LeadPiont) were placed to confirm the STN location and the superior and inferior borders, and then the treatment electrodes were implanted. Patients in case 1 and case 3 had 3389 electrodes (Medtronic) and patient in case 2 had PINS L301 electrodes (Tsinghua Pinch). After intraoperative electrical stimulation, the patient’s dystonia symptoms improved without adverse effects, and 1.5T MRI was repeated after closing the incision to confirm that the electrodes were located in the STN nucleus. Under general anesthesia, a 5x125px subcutaneous pocket was made below the clavicle, and the pulse generator (Case 1 and Case 3: Activa, Medtronic; Case 2: PINS G101, Tsinghua Pinch) was implanted subcutaneously in the chest and connected to the treatment electrode through an extension wire. All three patients did not have any surgery-related complications. 3. Efficacy assessment: The BFM dystonia rating scale (BFMDRS), including the movement scale and the dysfunction scale, was used for preoperative and postoperative scoring. The improvement rate of symptoms was calculated by the following formula: improvement rate = (preoperative score – postoperative score)/preoperative score × 100%. Case 1 patient was turned on the stimulator 10 days after surgery, with monopolar stimulation (C+, 1-, 2-), stimulation parameters: voltage 2.5V, frequency 130Hz, pulse width 60μs. The symptoms of involuntary movement of the right upper limb and involuntary head shaking were relieved, but there was still difficulty in head uprightness. The improvement rate was 97%, and the BFMDRS-M score was still 0.5 at the 12-month follow-up. At the current follow-up of 24 months, the improvement rate is still maintained at 97% with satisfactory symptom control and no further adjustment of stimulation parameters. Case 2 patient was turned on 12 days after surgery with monopolar stimulation (left IPG: C+, 3-, 150Hz, 60μs, 1.7V; right IPG: C+, 3-, 150Hz, 90μs, 2V). After turning on the machine, muscle tone was normal, walking difficulty and abnormal postural gait improved, and the restorative tablets were discontinued. The symptoms further improved 1 month after surgery, and the BFMDRS-M score decreased from 54 to 25, with an improvement rate of 54%; the BFMDRS-M score was 20 at the 2-month follow-up after surgery, with an improvement rate of 63%. There was no aggravation of symptoms after discontinuation of Benadryl, and basically returned to normal work, taking alprazolam 2 tablets/time, 3 times/day at work and no need to take it at rest. Patients’ basic living behaviors such as walking, eating, dressing and bathing were significantly improved. Case 3 patient was started 12 days after surgery with monopolar stimulation (C+, 0-) with stimulation parameters: voltage 2.6V, frequency 150Hz, pulse width 90μs. 1 week left upper limb stiffness was slightly relieved compared to preoperative, muscle tone was about 3 levels higher. 1 month later it was changed to double contact monopolar stimulation (C+, 1-, 0-) with stimulation parameters: voltage 1.6V, frequency 120Hz, pulse width 60μs. 1 month after surgery BFMDRS-M The BFMDRS-M score decreased from 17 to 9 at 1 month after surgery, with an improvement rate of 37%; the BFMDRS-M score remained at 9 at the 2-month postoperative follow-up. The patient was able to partially extend the palm of the left hand, lift the left hand to level the shoulder, and straighten the left elbow. III. Discussion With the obvious efficacy of DBS in the treatment of Parkinson’s disease, people began to apply this technique to the treatment of dystonia. Ostrem et al [1] summarized the literature on the use of DBS for the treatment of dystonia up to 2008 and reported that the improvement rate of primary dystonia was 21-95%, with most of the reported improvement rates being 60-70%. The stimulation current is also generally larger than in the treatment of Parkinson’s disease, with most reports using pulse widths >180 μs and requiring higher frequencies (130C185 Hz). Therefore, the duration of battery exchange is usually 1-2 years. Isaias et al [2] reported 30 patients with primary generalized dystonia treated with Gpi- DBS: 30 with 2 years of follow-up (82.5%), 23 with 3 years (85.5%), 13 with 4 years (84.7%), 9 with 5 years (83%), 5 with 7 years (82%), and 1 with 8 years (98.8%). (98.8%).Egidi M et al [3] retrospectively analyzed 69 patients with dystonia, primary and secondary, generalized and focal, treated with DBS at 7 Italian neurosurgical centers as of 2005, targeting GPi, with a mean preoperative duration of 17 years and a mean postoperative follow-up of 3-84 months, with a mean BFM improvement rate of 42% (0-92%) in 45% for primary and 37% for secondary, with a better outcome for DYT1 gene positivity; secondary patients had a very good outcome for drug-induced. Preoperative disease duration was negatively correlated with outcome. a meta-analysis by Andrews et al [4] of 209 patients with primary dystonia treated with DBS reported in the literature found significantly higher improvement rates in patients with short preoperative disease duration, low preoperative scores (milder disease) and DYT1+. 91 DYT1+ patients had an improvement rate of 67.5% (53.3%-92.3%) and The improvement rate was 55.8 % (38.6-79.3 %) in 108 DYT1 gene-negative patients and 51.9 % (20.8-71.4 %) in 10 patients with unknown DYT1 information, but significant improvement was seen in both DYT1+ and DYT1- patients.Holloway et al [5] analyzed 24 publications with BFM scores for a total of 137 patients receiving The mean BFM improvement rate was 51.8% (34-100%) in patients treated with DBS, with better stimulation of the GPi than the ventral posteromedial thalamus and poorer efficacy in those with cerebral palsy and those caused by encephalitis.Lee J et al [6] summarized the literature and concluded that compared to DBS for Parkinson’s disease, DBS for dystonia is slower to show efficacy, requires higher voltage, and the setting of stimulation parameters is more individualized. Given the experience of STN-DBS in significantly improving dyskinesia and dystonia in Parkinson’s disease, STN-DBS for dystonia has attracted widespread attention in recent years [7-9,11-12]. Zhang et al [7] first reported STN-DBS for late-onset dystonia, and patients had 92% improvement rate at 3-month follow-up. Zhang et al [8] reported 8 patients with primary dystonia undergoing STN-DBS with a satisfactory improvement rate of BFM of 40%-90% at 6-month follow-up. Recently, Cao Chunyan et al [9] also achieved satisfactory results in the long-term follow-up of 27 patients with primary dystonia treated with STN-DBS: the improvement rates of BFM were 55%, 77%, and 79% at 1, 3, and 10 years of follow-up, respectively; the quality of life improved significantly after 1 month, further improved after 1 year, and maintained stable thereafter. Although there are not many reported cases of STN-DBS for dystonia, the results generally agree that STN is a very effective target for the treatment of dystonia. it often takes weeks to months to show improvement in dystonia symptoms after GPi-DBS, whereas STN-DBS shows partial symptom relief at the stage of temporary electrical stimulation outside the body, suggesting a more sensitive response to STN-DBS. sensitive, facilitating the selection of optimal stimulation parameters as soon as possible. In addition, the STN volume is smaller than the GPi and the stimulation parameters are set at lower values, prolonging the battery life of the stimulator and reducing the financial burden on the patient. battery life was 5.5 ± 1.1 years (personal communication). Schjerling et al [11] found in a randomized double-blind crossover trial of 12 patients that STN showed a more significant improvement in BFM motor scores than Gpi stimulation for dystonia (STN 13.8 points, n=12; GPi 9.1 points, n=7, p=0.08). Due to the small number of cases, the authors concluded that it is not yet possible to conclude that STN is more suitable than GPi for the treatment of dystonia, but concluded that STN is a safe and promising target for the treatment of dystonia. Our results also show that STN-DBS for dystonia can achieve significant efficacy and can be maintained in the long term. For postoperative program control, we selected the stimulation contacts with reference to the postoperative cranial MRI electrode position and the effect of test contact stimulation; the principles of stimulation parameter setting were: maximum stimulation that did not cause patient discomfort (when no significant improvement was seen with stimulation) and minimum effective stimulation (when improvement was seen with stimulation). Schjerling et al [11] in their randomized double-blind study, all at 130 Hz, GPi2.8 ± 0.2 V, 116.3 ± 18.0 msec; ST2.6 ± 0.2 V, 60.0 msec. Both our experience and the literature suggest a more individualized parameter setting for DBS for dystonia.