Abstract
Introduction
We present our surgical complications resulting in neurological deficit or additional surgery during 25 years of DBS of the subthalamic nucleus (STN) for Parkinson’s disease (PD).
Methods
We conducted a retrospective chart review of all PD patients that received STN DBS in our DBS center between 1998 and 2023. Outcomes were complications resulting in neurological deficit or additional surgery. Potential risk factors (number of microelectrode recording tracks, age, anesthesia method, hypertension, and sex) for symptomatic intracerebral hemorrhage (ICH) were analyzed. Furthermore, lead fixation techniques were compared.
Results
Eight hundred PD patients (507 men, 293 women) received unilateral (n = 11) or bilateral (n = 789) implantation of STN electrodes. Neurological deficit due to ICH, edema, delirium, or infarction was seen in 8.4% of the patients (7.4% transient, 1.0% permanent). Twenty-two patients (2.8%) had a symptomatic ICH following STN DBS, for which we did not find any risk factors, and five had permanent sequelae due to ICH (0.6%). Of all patients, 18.4% required additional surgery; the proportion was reduced from 27% in the first 300 cases to 13% in the last 500 cases (p < 0.001). The infection rate was 3.5%, which decreased from 5.3% in the first 300 cases to 2.2% in the last 500 cases. The use of a lead anchoring device led to significantly less lead migrations than miniplate fixation.
Conclusion
STN DBS leads to permanent neurological deficit in a small number of patients (1.0%), but a substantial proportion needs some additional surgical procedure after the first DBS system implantation. The risk of revision surgery was reduced over time but remained significant. These findings need to be discussed with the patient in the preoperative informed consent process in addition to the expected health benefit.
Keywords: Parkinson’s disease, Deep brain stimulation, Subthalamic nucleus, Postoperative complications, Cerebral hemorrhage
Introduction
Deep brain stimulation (DBS) is an established treatment for patients with Parkinson’s disease (PD) who despite optimal pharmacological treatment suffer from motor response fluctuations. DBS treatment for PD reduces motor symptoms, improves quality of life, and facilitates dopaminergic medication reduction [1–3]. Most studies in DBS for PD focus on reduction of motor symptoms, expressed in MDS-UPDRS motor examination (ME) score [4]. However, possible complications of DBS surgery can be a reason for patients to withhold from this elective treatment option. Surgical benefit and risk are equally important for preoperative shared decision-making and it is essential to know the risk of complications in DBS surgery, in addition to the positive health benefit [5]. Therefore, we evaluated the incidence of surgical complications after subthalamic nucleus (STN) DBS surgery for PD, which caused either temporary or permanent neurological deficit or required additional surgery in the past 25 years in our DBS center.
The potentially most harmful surgical complication is intracerebral hemorrhage (ICH) induced by electrode placement. The number of microelectrode recording (MER) trajectories, age at surgery, anesthesia method, hypertension, and sex are possible risk factors for ICH after electrode placement [6–9]. And we will investigate if these previously reported risk factors for ICH could be confirmed. In addition, we will evaluate the role of lead anchoring devices in reducing vertical lead migration in our sample and we evaluate the change in complication frequency over time while the surgical group gained more experience.
Methods
We conducted a retrospective single-center cohort study on all PD patients who received STN DBS surgery between 1998 and 2023. We assessed all the clinical admissions and outpatient clinic visits following STN DBS surgery by means of a full chart review. Patients visited the outpatient clinic for DBS programming and adjustments of medication by neurologists and DBS-nurse specialists at regular intervals, and attention for side effects and/or surgical complications were fixed items during these visits.
DBS Procedure
Over the past 25 years, we have made several adaptations in our surgical workflow due to technical and imaging developments: (a) frame-based MRI was replaced by fusion of preoperative higher field strength MRI with stereotactic intraoperative cone beam CT (iCBCT); (b) the number of trajectories for MERs was reduced from five to usually one or two based on increased image quality and gained experience; (c) lead fixation to the skull is performed by the commercially available anchoring devices, rather than miniplates as in the beginning; and (d) surgery under local anesthesia was replaced by general anesthesia. Our current STN DBS workflow starts with general anesthesia followed by frame fixation. Hereafter, the stereotactic iCBCT is acquired and coregistered with the preoperative 3 Tesla (3T) T1 sequence. Other 3T and 7T sequences are subsequently coregistered to the 3T T1 sequence. The target coordinates and trajectory are calculated using Brainlab software (Brainlab AG, Munich, Germany). A C-shaped frontal incision is used to ensure the burr hole and lead anchoring device are entirely covered by the small skin flap. MER is executed by temporarily ceasing propofol infusion, while the patient continues to sleep on remifentanil only. Before starting the MER, the minimal time of propofol discontinuation is 20 min. The MER guide tube is then replaced for the final electrode. This procedure is repeated on the contralateral side. After final electrode placement, the propofol is resumed; electrode placement accuracy is directly verified with a second intra-operative iCBCT after which the frame is removed from the skull. In the same procedure, the electrodes are then connected to subcutaneous extensions and a subcutaneous or submuscular, infraclavicular implantable pulse generator (IPG). Additional postoperative CT scans were not obtained routinely.
Outcome Measures
Here we report all complications that led to transient or permanent neurological deficit, required revision surgery, or death. Transient neurological deficit was defined as deficit that was reported by the nurse specialist or neurologist and from which the patient had fully recovered in later follow-up visits. Permanent neurological deficit was defined as deficit that did not fully subside, or when it was unclear whether the patient fully recovered due to loss of follow-up. Revision surgery with replacement of electrodes due to poor/no effect was offered in case of (a) less than 30% MDS-UPDRS ME score improvement in the off-medication on-DBS state in best DBS programming settings, compared to the pre-operative off-medication state MDS-UPDRS ME score, or (b) a small therapeutic window due to stimulation-induced side effects. In addition, the patient needed to be unsatisfied of the DBS treatment effect and willing to undergo revision surgery. We further analyzed neurological deficits caused by an ICH, for which we investigated possible risk factors (number of MER trajectories, age, anesthesia method, hypertension, sex).
We took into consideration that there could be a development over time in complication rates due to the learning curve of the neurosurgical team with growing personal experience and due to the fine-tuning of the surgical workflow with technical developments in imaging, stereotactic hardware, and lead anchoring techniques. Furthermore, we were also interested in a present-day complication rate reflecting the current practice at our site. Therefore, we arbitrarily divided this cohort between the first 300 patients treated roughly in the period wherein our current DBS procedure was shaped to how we perform it today, versus the 500 patients treated thereafter. Two members of the surgical team were present throughout the whole series (P.R.S., P.v.d.M.) and two joined the team later (M.B., R.H.) when the current workflow was established.
Statistical Analysis
Statistical analysis was performed using IBM SPSS Statistics for Windows (version 28.0. IBM Corp., Armonk, NY, USA). All complication risks were analyzed per patient. Lead migration and ICH were also analyzed per electrode. Continuous variables were analyzed using student’s T test. Dichotomous and categorical variables were analyzed using χ2 test or Fisher’s exact test for small sample sizes. For the comparison of the number of MER trajectories with the incidence of symptomatic ICH, the χ2 test, Fisher’s exact test, and Fisher-Freeman-Halton exact test were used. No multivariate regression analysis was conducted. A p value <0.05 was considered statistically significant.
Results
Eight hundred PD patients (507 men, 293 women) underwent STN DBS surgery between April 1998 and January 2023. The mean (±SD) age at the time of surgery was 61.1 ± 8.4. The median follow-up duration after surgery was 55 months (interquartile range: 29–95). Out of the 800 PD patients, 744 were still alive at the end of this study period and therefore possibly subject to future complications. The implants used were Medtronic (Medtronic plc, Dublin, Ireland), St. Jude Medical (St. Jude Medical, Inc., Saint Paul, MN, USA), and Boston Scientific (Boston Scientific Corporation, Marlborough, MA, USA). The baseline characteristics are shown in Table 1.
Table 1.
Baseline characteristics
| Agea, mean (SD) | 61.1 (8.4) |
| Sex, male, N (%) | 507 (63) |
| Disease durationa, mean (SD), years | 11.3 (5.1) |
| Follow-up duration, median [IQR], months | 55 [29–95] |
| Laterality electrode placement, N (%) | |
| Bilateral | 773 (97) |
| Staged bilateral | 16 (2) |
| Unilateral | 11 (1) |
| MERs used, N (%) | 674 (84) |
| Anesthesia method, N (%) | |
| Awake | 487 (61) |
| Asleep | 313 (39) |
IQR, interquartile range.
aAt the time of surgery.
In this cohort, 67 (8.4%) of the PD patients receiving STN DBS were affected by one or more intracranial complications causing neurological deficit due to ICH, delayed onset edema, infarction, or postoperative delirium, which was transient in 7.4% and permanent in 1.0%. Furthermore, 147 (18.4%) of the patients required additional surgery at some point in the whole follow-up period after the initial operation due to infection, skin erosion, or another hardware-related issue such as repositioning of the lead or stimulator. An overview of all complications is shown in Table 2.
Table 2.
Complications
| Patients, N (%)a | Complications, N | |
|---|---|---|
| Intracranial | 118 (14.8) | 153 |
| Operation related | 87 (10.9) | 99 |
| Neurological deficit | 67 (8.4) | 75 |
| Permanent | 8 (1.0) | 9 |
| Transient | 59 (7.4) | 66 |
| Symptomatic ICH | 22 (2.8) | 22 |
| Infarction | 1 (0.1) | 1 |
| Delayed onset edema | 13 (1.6) | 13 |
| Deliriumb | 34 (4.3) | 34 |
| Seizuresb | 5 (0.6) | 5 |
| Poor/no effect due to electrode malposition | 23 (2.9) | 24 |
| Lead revision | 17 (2.1) | 18 |
| Additional lesioning surgery | 3 (0.4) | 3 |
| Extra lead placement | 3 (0.4) | 3 |
| Hardware related – lead | 39 (4.9) | 55 |
| Revision lead | 24 (3.0) | 25 |
| Lead migration with poor/no effect | 17 (2.1) | 18 |
| Electrical dysfunctionc | 7 (0.9) | 7 |
| Infection/erosion | 16 (2.0) | 30 |
| Removald | 15 (1.9) | 15 |
| Reimplantation | 14 (1.8) | 15 |
| Extracranial | 109 (13.6) | 173 |
| Operation related | 31 (3.9) | 32 |
| Hematoma IPG | 31 (3.9) | 32 |
| Hardware related – extensions/IPG | 86 (10.8) | 141 |
| Revision | 62 (7.8) | 88 |
| Electrical dysfunctionc | 19 (2.4) | 22 |
| Disconnection | 5 (0.6) | 5 |
| Iatrogenic damage | 9 (1.1) | 9 |
| Repositioning (pain) | 39 (4.9) | 52 |
| Infection/erosion | 27 (3.4) | 53 |
| Wound debridement/revision | 6 (0.8) | 15 |
| Removal | 14 (1.8) | 18 |
| Reimplantation | 11 (1.4) | 12 |
| Relocation | 8 (1.0) | 8 |
ICH, intracerebral hemorrhage; IPG, implantable pulse generator.
aSum of all percentages exceed 100% since some patients experienced multiple complications.
bNot caused by ICH.
cSome or all stimulation contacts unusable with high impedances or short circuit due to damage of some or all of the electrical wires in the lead or extension.
dHardware removal of the complete DBS system was counted once under intracranial complications.
The number of patients requiring revision surgery was 82 (27.3%) in the first 300 patients compared to 65 (13.0%) in the last 500 patients (p < 0.001). The risks for almost all causes of revision surgery were reduced significantly in the last 500 patients, except for hardware malfunction and IPG hematoma (Table 3).
Table 3.
Surgical learning curve
| Total 800 patients, N (%) | First 300 patients, N (%) | Last 500 patients, N (%) | OR (95% CI) | p value | |
|---|---|---|---|---|---|
| Revision surgery | 147 (18.4) | 82 (27.3) | 65 (13.0) | 0.40 (0.28–0.57) | <0.001 |
| Infection | 27 (3.4) | 16 (5.3) | 11 (2.2) | 0.40 (0.18–0.87) | 0.02 |
| Erosion/wound dehiscence | 12 (1.5) | 9 (3.0) | 3 (0.6) | 0.18 (0.05–0.64) | 0.003 |
| Poor/no effecta | 23 (6.0) | 14 (4.7) | 9 (1.8) | 0.04 (0.16–0.88) | 0.02 |
| Lead migration | 17 (12.1) | 12 (4) | 5 (1.0) | 0.24 (0.09–0.70) | 0.004 |
| Hardware malfunctionb | 31 (3.9) | 16 (5.3) | 15 (3.0) | 0.55 (0.27–1.13) | 0.10 |
| IPG hematoma | 31 (3.9) | 16 (5.3) | 15 (3.0) | 0.55 (0.27–1.13) | 0.10 |
| Pain | 39 (4.9) | 21 (7) | 18 (3.6) | 0.50 (0.26–0.95) | 0.03 |
Sum of all percentages exceed 100% since some patients experienced multiple complications.
aWithout lead migration.
bDisconnection, iatrogenic damage, and electrical dysfunction.
Symptomatic ICH
Out of 800 PD patients, 22 (2.8%) patients had a symptomatic ICH following STN DBS. Symptomatic ICH was left sided in 71.4% and right sided in 23.8%. One patient had a bilateral symptomatic ICH. Eighteen ICHs (82%) were more superficial (sub)cortical and four (18%) were deep in the basal ganglia. Five (0.6%) patients suffered permanent neurological deficit due to an ICH.
A 56-year-old male developed a right-sided subcortical ICH after STN DBS surgery, resulting in a left-sided hemiparesis, from which he partially recovered in the following days. On day 9, the patient developed an acute worsening of the hemiparesis caused by cerebral infarction. The patient partially recovered but remained wheelchair dependent. A 75-year-old female developed an intraventricular hematoma after postoperative heparin admission for atrial fibrillation. She experienced a right-sided hemiparesis with hemianopia, which recovered, but she had a substantial permanent cognitive disorder. A 67-year-old female suffered from a postoperative right-sided ICH in the basal ganglia resulting in a left-sided hemiplegia from which she did not recover. A 55-year-old female developed diplopia due to a postoperative right-sided ICH in the basal ganglia, which did not subside. A 60-year-old female patient suffered from a postoperative ICH in the left subthalamic nucleus resulting in dysarthria and a balance disorder, with no signs of recovery. The 16 patients with transient neurological deficit due to an ICH experienced aphasia, speech initiation disorder, dysarthria, central facial palsy, paresis of the left hand, frontal lobe syndrome, delirium, and cognitive decline. These resolved within 6 months after surgery in 12 patients, within the first year in 1 patient, and in 3 patients we could not retrieve the duration of the recovery phase from the charts.
Risk Factors of ICH
In the per patient analysis, we found no significant effect of total number of MER trajectories versus the incidence of a symptomatic ICH (p = 0.387). There was also no significant difference found in the incidence of a symptomatic ICH between groups with different numbers of MER trajectories in the per electrode analyses (Table 4). When we focused on the last 500 patients, the only statistically significant effect found was the higher risk on developing an ICH in the patients who received no MER versus the patients with only one MER trajectory (online suppl. Table 1; for all online suppl. material, see https://doi.org/10.1159/000539483).
Table 4.
Number of MER trajectories per electrode in relation to ICH
| MER tracks, n | Total electrodes, n (%) | No ICH | ICH, n (%) | OR (95% CI) | p valuea |
|---|---|---|---|---|---|
| 0 (no MER) | 227 (14.2) | 222 | 5 (2.2) | ||
| 1 | 349 (21.9) | 347 | 2 (0.6) | 0.26 (0.49–1.33) | 0.12 |
| 2 | 309 (19.4) | 306 | 3 (1.0) | 0.44 (0.10–1.84) | 0.29 |
| 3 | 502 (31.6) | 496 | 6 (1.2) | 0.54 (0.16–1.78) | 0.33 |
| 4 | 106 (6.7) | 104 | 2 (1.9) | 0.85 (0.16–4.47) | 1.00 |
| ≥5 | 73 (4.6) | 71 | 2 (2.7) | 1.25 (0.24–6.58) | 0.68 |
| Missing | 23 (1.4) | 21 | 2 (8.7) | ||
| Total | 1,589 | 1,567 | 22 (1.4) |
ICH, intracerebral hemorrhage.
aMER 0 = reference.
There was no statistically significant difference found in age, anesthesia method, patients with antihypertensive medication, and/or insufficiently managed chronic hypertension in their medical history, or sex, between the group with a symptomatic ICH and the group without a symptomatic ICH (online suppl. Table 2). Because of the small incidence of a symptomatic ICH (n = 22), it was not possible to conduct a multivariate logistic regression model.
Infection
An infection requiring surgery was seen in 27 (3.4%) patients. These 27 patients required 83 operations in total. Most patients with an infection required removal of the hardware, antibiotic treatment, and in a later stage reimplantation of the DBS hardware. The infection rate in our first 300 patients was 5.3% versus 2.2% in the 500 patients following as shown in Table 3.
Lead Migration
In total, 17 (2.1%) patients had lead revision surgery due to lead migration. The incidence of lead migration per patient was significantly lower when a lead anchoring device (1.1%) was used versus miniplate fixation (6.3%) per patient (OR: 0.16, 95% CI: 0.06–0.4, p < 0.001). This effect remained when analyzed per electrode. Out of 1,281 electrodes fixated with an anchoring device, seven leads (0.5%) migrated versus 13 (4.2%) lead migrations out of 308 electrodes that were fixated with a miniplate (OR: 0.15, 95% CI: 0.05–0.32, p < 0.001) (online suppl. Table 3).
Delayed Onset Edema
Thirteen (1.6%) patients experienced, most often transient, symptoms due to delayed onset edema. Temporary symptoms of delayed onset edema were cognitive decline, dysarthria, apraxia, speech difficulties, apathy, confusion, and delirium. One patient experienced seizures with loss of consciousness and intensive care unit admission from which he had a full recovery. Only 1 patient had permanent mild cognitive impairment due to delayed onset edema. Delayed onset edema occurred only in the last 500 patients; 12 times (3.1%) in 390 patients with segmented leads; and once (0.9%) in 110 patients with conventional ring electrodes.
Death
In this cohort, we had one death within 30 days after surgery. This was a 72-year-old woman with very advanced PD who had an in-hospital cardiac arrest the night following surgery for IPG replacement. Another death occurred 4 months after DBS surgery as a sequel to a hip fracture and was not considered related to DBS [10]. Data on the cause of death of the other 54 patients who deceased more than 6 months after the DBS implantation in this cohort are incomplete, but these were not deemed related to DBS by the notifying physician or family.
Discussion
In this retrospective analysis, we documented the surgical complications after STN DBS surgery for PD resulting in neurological deficit or leading to additional surgery in our large sample of consecutively treated patients, which is key information for the preoperative process of shared decision-making. In this cohort, 8.4% of the patients suffered from postoperative neurological deficit, most frequently transient by nature. The most common neurological deficit was a delirium (4.3%) followed by a symptomatic hemorrhage. The incidence of postoperative delirium in this cohort is lower than reported in the literature (5.8–42.6%) [11]. This could be a result of underreporting since not all patients underwent a standardized postoperative delirium scale assessment. However, in the recent trial in our DBS center comparing awake versus asleep STN DBS, 110 PD patients had a standardized postoperative delirium assessment and only 4% of the patients in the awake STN DBS group and 2% in the asleep STN DBS group had a postoperative delirium, comparable with the incidence in our overall cohort [10]. Prolonged hospital stay can be a risk factor for a delirium [12]. In order to minimize the incidence of postoperative delirium, we try to keep the hospital stay as short as possible and most patients are discharged on the day following DBS surgery.
The incidence of symptomatic ICH after DBS surgery (2.8%) was comparable to the incidence found in the literature (2.1%) [13]. There is a continuing discussion on the use of MERs and studies have shown that multiple MER tracks can increase the risk of ICH [14]. Although there is a trend in a higher risk of ICH with an increasing number of MER tracks used in our sample, we did not find a statistically significant effect. It is possible that this reflects a lack of power due to low numbers. However, MER was not used in 14.5% of the cases, usually for logistical reasons or technical failure, and in these patients, ICH occurred more often than in patients where 4 or fewer MER tracks were used. This may be due to the fact that in these patients, the Leksell macroelectrode was used to create the track, which has a larger diameter than the cannulas used for MER, making the mechanical impact of electrode introduction at the cortical surface larger, as the majority of ICH is (sub)cortical and not in the depth. Moreover, we did not find the incidence of postoperative ICH to be related to a medical history of hypertension, male sex, or age, even though these factors were previously shown to be risk factors [15]. In order to minimize postoperative ICH after STN DBS, we avoid all vessels as visible on contrast-enhanced T1 MRI sequences during the preoperative trajectory planning. Furthermore, we plan the trajectory entry on top of a sulcus and apply fibrin glue in the burr hole, in order to minimize brain shift due to cerebral spinal fluid leakage. We like to point out that the rate of ICH reported here cannot automatically be extrapolated to other DBS targets used in PD such as the globus pallidus or the thalamus, although the majority of hemorrhages were located (sub)cortically, for which the risk is probably very similar between targets.
Our overall percentage of revision surgery due to a complication (18.4%) is comparable with the incidence reported by Bouwens et al. [16] (18.5%) but much higher than the incidence reported by Jung et al. [17] (6.1%). When we take into account the learning curve of the DBS team and advancements in imaging and hardware over time, revision surgery was significantly higher in the first 300 patients than in the last 500 patients. The most common indication for revision was pain, caused by tethering of the extension wire or rotation of the IPG. During revision surgery, the extension wire can be replaced by a new flexible extension and attention is paid to position the extension wire in a deeper subcutaneous layer. In order to prevent pain and erosion at the IPG site, we increasingly place the IPG in the submuscular instead of the subcutaneous space.
Surgical site infection after STN DBS surgery is one of the most frustrating complications. In many cases, it cannot be resolved with debridement, and all hardware involved must be removed. The infection rate in this cohort (3.4%) was just below the range reported in previous studies (4.7–5.1%) [18–20]. In the most current 500 operated patients, this incidence dropped to 2.2%. In this cohort, 27 patients required 83 revision surgeries for infection. The optimal strategy from a surgical point of view is removal of all hardware followed by antibiotic treatment and then reimplantation, requiring two additional surgeries. However, in early-stage infections sometimes we only removed the affected part of the DBS system, which can be successful and prevent an invalidating DBS withdrawal syndrome [21]. Unfortunately, the infection may have spread already to another part of the system, or after antibiotic treatment the infection can return, requiring several additional surgeries to obtain a “clean” DBS system again. In order to prevent surgical site infections, all our patients receive intravenous preoperative antibiotics prophylaxes, 2 g cefazolin, 30 min prior to surgery. They do not receive any postoperative prophylaxes.
Poor/no effect due to lead malposition was seen in 40 patients (5.0%). In 17 out of 40 cases (2.1%), the malposition was caused by lead migration. This is a higher rate of lead migration than reported in the meta-analysis of Cabral et al. [22] (1.3%). This can partially be explained by the homogenous group of fixation techniques in this cohort. We found a significant difference in lead migration between our current method of lead fixation using a lead anchoring device compared to the abandoned method of miniplate fixation, strongly favoring the adoption of lead anchoring devices.
Symptomatic delayed onset edema was seen in 1.6% of the patients. This rate is lower than reported in the literature (3.1%) [23]. Even though edema can result in a severe clinical course, it is mostly self-limiting. In this cohort, all but 1 patient fully recovered from their symptoms. It is noteworthy that 12 of our 13 patients with delayed onset edema had segmented leads implanted, which comprises 3.1% of the 390 patients with segmented leads, and a higher occurrence of delayed edema in segmented leads compared to conventional ring electrodes was reported before [24]. However, we also only became increasingly aware of this phenomenon in the last decade [25], in the time period where nearly all our patients received segmented leads. We perform a direct postoperative CT scan for electrode localization and no routine postoperative imaging in the days after surgery, so it is well possible that the occurrence of delayed edema was largely underestimated in the past due to its self-limiting nature. Further reports with routine imaging several days after surgery from a cohort where both types of electrodes were implanted are necessary to address this issue [26].
With regard to implantation of DBS electrodes under local anesthesia to enable test stimulation or the use of general anesthesia throughout the whole procedure, practice still varies widely between different centers. Since 2019, awake STN DBS has been abandoned in our center after the GALAXY trial in which asleep and awake electrode implantation were compared. In this trial, there was no difference between the two groups in terms of cognitive, mood, and behavioral adverse effects nor in symptomatic improvement [10]. This corroborated the meta-analysis conducted by Liu et al. [27] and Ho et al. [28], who found no significant differences in motor symptom reduction after asleep or awake DBS surgery for PD patients. In the trial, we reported more symptomatic ICH in PD patients who were operated asleep compared to awake, but this was a random finding, and in our overall cohort reported here we found no statistically significant difference in the incidence of ICH between patients operated awake versus patients who were operated asleep, which is not surprising as the invasiveness and associated risk of the two procedures are not different.
There are several limitations to this study. The retrospective design with chart review has the inherent risk of loss of data due to incomplete filing. It is possible that nurse specialists failed to record some of the mild transient neurological deficits during outpatient visits. However, clear persistent neurological deficit and especially complications requiring surgery will probably not have been missed often. Patients lost to follow-up may have had additional surgery in another DBS center, although this is not common due to the short travel distances in the Netherlands. Furthermore, even though we selected one patient group and one DBS target, there is a heterogeneity within this cohort due to the long time span of data collection during which there were several adjustments in our surgical workflow.
In conclusion, we shared the complications from our surgical experience in 800 PD patients undergoing STN DBS. We found a small risk (1.0%) of developing permanent neurological deficit after surgery. We did not identify any risk factors (number of MER tracks, age, anesthesia method, hypertension, or sex) for the development of a symptomatic ICH. There was a clear development over time, with a significant reduction of the risk of revision surgery over the years, whereby growing experience led to reductions of infection and other wound problems, uncomfortable IPG placement, lead migration, and poor electrode placement. These incidences of adverse events need to be discussed with the patient in the preoperative informed consent process in addition to the expected health benefit.
Statement of Ethics
Ethical approval is not required for this study in accordance with national guidelines. The need for informed consent was waived by the medical ethical board of the Amsterdam University Medical Centers due to the retrospective nature of the study and anonymization in the data collection process. All patients gave written informed consent for publication of their demographic data.
Conflict of Interest Statement
PRS received unrestricted research support and speakers fees from Boston Scientific, Medtronic, and Elekta. R.d.B. received research grants from AMC Foundation, ROMO Foundation, Stichting ParkinsonFonds, and Medtronic, all paid to the institution. P.v.d.M. received a research grant from Amsterdam University Medical Centers for exploration of the effect of DBS in disorders of consciousness and arousal. R.H., Y.W., M.B., and D.V. declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Funding Sources
This study was not supported by any sponsor or funder.
Author Contributions
R.H.: conceptualization, investigation, methodology, data curation, formal analysis, validation, and writing – original draft and review and editing of the manuscript; Y.W.: investigation, data curation, and writing – original draft and review and editing; M.B. and R.d.B.: writing – review and editing; D.V.: methodology and formal analysis; P.S.: conceptualization, methodology, writing – original draft and review and editing, and supervision; and P.v.d.M.: conceptualization, data curation, and writing – review and editing of the manuscript.
Funding Statement
This study was not supported by any sponsor or funder.
Data Availability Statement
All data generated or analyzed during this study are included in this article and its supplementary material files. Further inquiries can be directed to the corresponding author.
Supplementary Material.
References
- 1. Williams A, Gill S, Varma T, Jenkinson C, Quinn N, Mitchell R, et al. Deep brain stimulation plus best medical therapy versus best medical therapy alone for advanced Parkinson’s disease (PD SURG trial): a randomised, open-label trial. Lancet Neurol. 2010;9(6):581–91. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Weaver FM, Follett K, Stern M, Hur K, Harris C, Marks WJ Jr, et al. Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial. JAMA. 2009;301(1):63–73. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Deuschl G, Schade-Brittinger C, Krack P, Volkmann J, Schafer H, Botzel K, et al. A randomized trial of deep-brain stimulation for Parkinson’s disease. N Engl J Med. 2006;355(9):896–908. [DOI] [PubMed] [Google Scholar]
- 4. Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, et al. Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord. 2008;23(15):2129–70. [DOI] [PubMed] [Google Scholar]
- 5. Bronstein JM, Tagliati M, Alterman RL, Lozano AM, Volkmann J, Stefani A, et al. Deep brain stimulation for Parkinson disease: an expert consensus and review of key issues. Arch Neurol. 2011;68(2):165. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Sansur CA, Frysinger RC, Pouratian N, Fu KM, Bittl M, Oskouian RJ, et al. Incidence of symptomatic hemorrhage after stereotactic electrode placement. J Neurosurg. 2007;107(5):998–1003. [DOI] [PubMed] [Google Scholar]
- 7. Seijo FJ, Alvarez-Vega MA, Gutierrez JC, Fdez-Glez F, Lozano B. Complications in subthalamic nucleus stimulation surgery for treatment of Parkinson’s disease. Review of 272 procedures. Acta Neurochir. 2007;149(9):867–76; discussion 76. [DOI] [PubMed] [Google Scholar]
- 8. Xiaowu H, Xiufeng J, Xiaoping Z, Bin H, Laixing W, Yiqun C, et al. Risks of intracranial hemorrhage in patients with Parkinson’s disease receiving deep brain stimulation and ablation. Parkinsonism Relat Disord. 2010;16(2):96–100. [DOI] [PubMed] [Google Scholar]
- 9. Zhang J, Wang T, Zhang CC, Zeljic K, Zhan S, Sun BM, et al. The safety issues and hardware-related complications of deep brain stimulation therapy: a single-center retrospective analysis of 478 patients with Parkinson’s disease. Clin Interv Aging. 2017;12:923–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. Holewijn RA, Verbaan D, van den Munckhof PM, Bot M, Geurtsen GJ, Dijk JM, et al. General anesthesia vs local anesthesia in microelectrode recording-guided deep-brain stimulation for Parkinson disease: the galaxy randomized clinical trial. JAMA Neurol. 2021;78(10):1212–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Li H, Han S, Feng J. Delirium after deep brain stimulation in Parkinson’s disease. Parkinsons Dis. 2021;2021:8885386. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. Stubljar D, Stefin M, Tacar MP, Cerovic O, Grosek S. Prolonged hospitalization is a risk factor for delirium onset: one-day prevalence study in slovenian intensive care units. Acta Clin Croat. 2019;58(2):265–73. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. Zrinzo L, Foltynie T, Limousin P, Hariz MI. Reducing hemorrhagic complications in functional neurosurgery: a large case series and systematic literature review. J Neurosurg. 2012;116(1):84–94. [DOI] [PubMed] [Google Scholar]
- 14. Rasiah NP, Maheshwary R, Kwon CS, Bloomstein JD, Girgis F. Complications of deep brain stimulation for Parkinson disease and relationship between micro-electrode tracks and hemorrhage: systematic review and meta-analysis. World Neurosurg. 2023;171:e8–23. [DOI] [PubMed] [Google Scholar]
- 15. Yang C, Qiu Y, Wang J, Wu Y, Hu X, Wu X. Intracranial hemorrhage risk factors of deep brain stimulation for Parkinson’s disease: a 2-year follow-up study. J Int Med Res. 2020;48(5):300060519856747. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16. Bouwens van der Vlis TAM, van de Veerdonk M, Ackermans L, Leentjens AFG, Janssen MLF, Kuijf ML, et al. Surgical and hardware-related adverse events of deep brain stimulation: a ten-year single-center experience. Neuromodulation. 2022;25(2):296–304. [DOI] [PubMed] [Google Scholar]
- 17. Jung IH, Chang KW, Park SH, Chang WS, Jung HH, Chang JW. Complications after deep brain stimulation: a 21-year experience in 426 patients. Front Aging Neurosci. 2022;14:819730. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18. Jitkritsadakul O, Bhidayasiri R, Kalia SK, Hodaie M, Lozano AM, Fasano A. Systematic review of hardware-related complications of deep brain stimulation: do new indications pose an increased risk? Brain Stimul. 2017;10(5):967–76. [DOI] [PubMed] [Google Scholar]
- 19. Kantzanou M, Korfias S, Panourias I, Sakas DE, Karalexi MA. Deep brain stimulation-related surgical site infections: a systematic review and meta-analysis. Neuromodulation. 2021;24(2):197–211. [DOI] [PubMed] [Google Scholar]
- 20. Bhatia R, Dalton A, Richards M, Hopkins C, Aziz T, Nandi D. The incidence of deep brain stimulator hardware infection: the effect of change in antibiotic prophylaxis regimen and review of the literature. Br J Neurosurg. 2011;25(5):625–31. [DOI] [PubMed] [Google Scholar]
- 21. Helmers AK, Kubelt C, Paschen S, Lubbing I, Cohrs G, Synowitz M. Can deep brain stimulation withdrawal syndromes be avoided by removing infected implanted pulse generator and cables with contralateral replacement in the same session? Stereotact Funct Neurosurg. 2021;99(5):377–80. [DOI] [PubMed] [Google Scholar]
- 22. Cabral AM, Pereira AA, Vieira MF, Pessoa BL, de Oliveira Andrade A. Prevalence of distinct types of hardware failures related to deep brain stimulation. Neurosurg Rev. 2022;45(2):1123–34. [DOI] [PubMed] [Google Scholar]
- 23. Tian Y, Wang J, Jiang L, Feng Z, Shi X, Hao Y. The need to be alert to complications of peri-lead cerebral edema caused by deep brain stimulation implantation: a systematic literature review and meta-analysis study. CNS Neurosci Ther. 2022;28(3):332–42. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24. Fricke P, Nickl R, Breun M, Volkmann J, Kirsch D, Ernestus RI, et al. Directional leads for deep brain stimulation: technical notes and experiences. Stereotact Funct Neurosurg. 2021;99(4):305–12. [DOI] [PubMed] [Google Scholar]
- 25. de Cuba CM, Albanese A, Antonini A, Cossu G, Deuschl G, Eleopra R, et al. Idiopathic delayed-onset edema surrounding deep brain stimulation leads: insights from a case series and systematic literature review. Parkinsonism Relat Disord. 2016;32:108–15. [DOI] [PubMed] [Google Scholar]
- 26. Giordano M, Innocenti N, Rizzi M, Rinaldo S, Nazzi V, Eleopra R, et al. Incidence and management of idiopathic peri-lead edema (IPLE) following deep brain stimulation (DBS) surgery: case series and review of the literature. Clin Neurol Neurosurg. 2023;234:108009. [DOI] [PubMed] [Google Scholar]
- 27. Liu Z, He S, Li L. General anesthesia versus local anesthesia for deep brain stimulation in Parkinson’s disease: a meta-analysis. Stereotact Funct Neurosurg. 2020;97(5–6):381–90. [DOI] [PubMed] [Google Scholar]
- 28. Ho AL, Ali R, Connolly ID, Henderson JM, Dhall R, Stein SC, et al. Awake versus asleep deep brain stimulation for Parkinson’s disease: a critical comparison and meta-analysis. J Neurol Neurosurg Psychiatry. 2018;89(7):687–91. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
All data generated or analyzed during this study are included in this article and its supplementary material files. Further inquiries can be directed to the corresponding author.