Hemorrhagic complications in deep brain stimulation: analysis of non-surgical risk factors in a cohort of 683 patients

Hemorrhagic complications in deep brain stimulation: analysis of non-surgical risk factors in a cohort of 683 patients | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Hemorrhagic complications in deep brain stimulation: analysis of non-surgical risk factors in a cohort of 683 patients Karol Sylwester Karamon, Michał Sobstyl, Łukasz Smoliński This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8575448/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 15 Apr, 2026 Read the published version in Neurosurgical Review → Version 1 posted 21 You are reading this latest preprint version Abstract Introduction Deep brain stimulation (DBS) is an established neurosurgical therapy for movement disorders, neuropsychiatric conditions, and drug-resistant epilepsy. Intracranial hemorrhage (ICH) remains among the most severe complications of DBS, with limited data on its risk factors. This study aims to assess the incidence of ICH and evaluate associated non-surgical and selected surgical risk factors in a large, single-center cohort. Methods We retrospectively analyzed 683 patients (1227 DBS electrodes implanted) treated at a single medical center between November 2008 and April 2025. Data on demographics, diagnoses, comorbidities, and surgical techniques were collected and analyzed using both statistical and descriptive methods to identify predictors of ICH. Hemorrhages were classified as symptomatic (transient or permanent) or asymptomatic based on clinical outcome. Results ICH occurred in 34 patients (4.98%), with 40 hemorrhagic events in total (3.26% per lead). Permanent neurological deficits occurred in 6 patients (0.9%). Antithrombotic therapy was the only statistically significant predictor of ICH in both univariate and multivariate models (OR = 4.14, p = 0.002; OR = 3.75, p = 0.006). Microelectrode recording (MER) and number of brain penetrations were associated with symptomatic ICH in univariate analysis but lost significance in multivariate models. No associations were found for sex, age, hypertension, diagnosis, or stereotactic target. Subthalamic nucleus targeting was observed exclusively in patients with permanent deficits. Conclusion DBS remains a safe procedure with low risk of permanent ICH-related morbidity. Antithrombotic therapy is a modifiable risk factor. Continued refinement in perioperative planning and surgical technique is essential to further minimize hemorrhagic risk. Deep Brain Stimulation Intracranial Hemorrhage Antithrombotic Therapy Functional Neurosurgery Introduction Deep brain stimulation (DBS) is a neurosurgical treatment method used to treat a spectrum of movement disorders, including Parkinson’s disease (PD), essential tremor (ET), and dystonia [ 1 ]. Additionally, DBS has proven effective in treating drug-resistant epilepsy (DRE) and neuropsychiatric disorders such as treatment-resistant obsessive-compulsive disorder (trOCD), treatment-resistant depression (TRD) and Tourette syndrome [ 2 , 3 ]. The procedure involves the precise implantation of DBS leads into deep brain nuclei using a stereotactic technique. The implantation is performed after placement of a stereotactic ring on the patient’s head, typically under local or general anesthesia [ 4 ]. Subsequently, using a neuronavigation system, the safest stereotactic trajectories from the brain surface to the target nuclei are planned, avoiding cerebral blood vessels, sulci, and ventricles [ 5 ]. Accurate placement of the DBS leads at the intended neurophysiological-neuroanatomical target is crucial for achieving optimal clinical outcomes. The implantation of DBS leads is inevitably associated with a risk of intracranial hemorrhage (ICH) [ 6 ]. Many publications have focused on surgical strategies and risk factors associated with minimizing the risk of ICH during DBS implantation. [ 7 – 9 ]. Less attention has been paid to non-surgical factors contributing to the development of ICH [ 10 ]. These factors include indication and duration of illness for DBS treatment as well as patients specific variables such as age at surgery, sex, presence of hypertension, and history of antithrombotics including antiplatelet or anticoagulant therapy [ 11 ]. The primary objective of the current study was to assess the prevalence of ICH and identify non-surgical risk factors for its development based on demographic and clinical data, including their evaluation in the overall patient population as well as in subgroups with symptomatic and asymptomatic ICH. In addition, selected surgical risk factors identified during the study are also presented. Methods Study design The study design involves a retrospective analysis of all 683 consecutive patients who underwent DBS surgery for movement disorders, neuropsychiatric disorders and drug-resistant epilepsy at the Department of Neurosurgery, Institute of Psychiatry and Neurology in Warsaw, Poland, from November 2008 to April 2025. Within the Institute of Psychiatry and Neurology, the regulations oblige researchers to regularly report all the complications of DBS procedures (Ethical Committee approval of Institute of Psychiatry and Neurology number 26/2023). The approval for reporting (publishing) all of the complications related to DBS procedures including ICH is valid for three years from the date of issuance. The necessity for acquiring additional written informed consent from the patients or their family members/caregivers was not required, given the retrospective nature of the study and the anonymization of personal data. The medical records of patients were reviewed, and data were collected using a standardized protocol. Data collected included demographic and clinical factors such as diagnosis, duration of symptoms, age at operation, gender, presence of hypertension and recent history of antiplatelet or anticoagulant therapy. Antiplatelet therapy included aspirin and/or P2Y12 receptor inhibitors, whereas anticoagulant therapy included vitamin K antagonists and direct oral anticoagulants. Together, these medications were classified as antithrombotic agents, all of which were discontinued at least 10 days prior to the planned DBS procedure in accordance with institutional perioperative protocols. In addition, surgical variables were also recorded, including the use of microelectrode recording (MER) and number of guiding electrodes utilized, type of implantation (bilateral simultaneous, bilateral staged, unilateral, or mixed), targeted stereotactic structure, type of anesthesia (general or local), and the manufacturer brand of the implanted system. We have analyzed only de novo DBS procedures. All reimplantation procedures due to DBS lead brakeage and DBS lead/s removal due to infection were excluded. Surgical DBS procedures For patients with PD, ET and other forms of non-ET movement disorders, a Leksell series G stereotactic frame was applied under local anesthesia, while general anesthesia was used for the patients with dystonia, neuropsychiatric disorders, Tourette syndrome or DRE. T2-weighted and T1-weighted 3D volumetric contrast-enhanced MRI scans were acquired on either a 1.5 Tesla or 3 Tesla magnet (Signa MRI Imaging Scanner, General Electric). Stereotactic G or Vantage frame (Elekta, Instruments, Stockholm, Sweden) were used. Following local/general anesthesia, the stereotactic head frame was secured to the patient’s skull, and contrast-enhanced CT scans with a slice thickness of 1.25 mm were obtained. These CT and MRI images were then transferred to surgical planning software; Brainlab (Brainlab iPlan 3.0.6, AG, Munich, Germany) or (Framelink S8, StealthStation, Medtronic, Minneapolis, MN, USA). The anesthesiologist kept intraoperative blood pressures below 130/80 mmHg during DBS procedures and < 140/90 mmHg after the surgery. The burr hole was typically placed 3.5 to 5 cm lateral to the midline in close proximity to or at the coronal suture level, targeting vessel-free surface of the frontal gyrus. The lead anchoring system at the burr hole was used in all patients (from different manufactures Medtronic, Bostonsientific less frequently Abbott). The dura was coagulated and sharply opened only at the point of stereotactic trajectory. In MER-guided procedures, usually three microelectrodes per hemisphere were inserted with the aid of the microdrive attached to the Leksell stereotactic arc. The 4-channel Lead point system (Medtronic) was used in MER-based procedures. Macrostimulation was subsequently performed using the dedicated macro tip constituting an integral part of the used microelectrode. Following determination of the clinically most optimal stimulation spot, the microelectrodes were withdrawn and the permanent DBS lead(s) were implanted. In non-MER-based DBS procedures, one guiding MER cannula (FHC, United States) was introduced to the stereotactic target. The depth of the guiding cannula was checked by lateral fluoroscopy. Thereafter, the guiding MER cannula was replaced by permanent DBS electrode which was introduced to the stereotactic target under lateral fluoroscopic guidance. Bipolar or monopolar stimulation were done through the quadripolar DBS lead using the external clinician Medtronic programmer. The implantable pulse generators (IPGs) were implanted in general anesthesia during the same operative session. Postoperative Imaging and ICH assessment All patients underwent postoperative CT examination following DBS procedures. Between November 2008 and December 2017, postoperative CT scans were obtained predominantly within the first 24 hours after surgery, with the majority performed within the first 12 hours. From January 2018 onward, CT imaging was performed intraoperatively with the stereotactic Leksell G or Vantage head frames in place, and delayed postoperative CT was not routinely performed unless clinically indicated. The location of each intracranial hemorrhage and its temporal relationship to the implantation procedure were recorded in all cases. Hemorrhages were classified as either asymptomatic or symptomatic. Asymptomatic hemorrhages produced no neurological symptoms. Symptomatic hemorrhages were further categorized as “transient” and defined as transient and mild symptoms lasting fewer than seven days or “permanent” involving permanent or long-lasting neurological deficits or mental status changes persisting for more than seven days. Statistical analysis Descriptive statistics, including means with standard deviations (SD) for continuous variables and counts with percentages for categorical variables, were used to summarize patient and procedural characteristics. To examine the association between ICH and selected clinical and surgical predictors, we applied Firth’s penalized likelihood logistic regression. This method reduces bias in analyses involving rare events, such as ICH following DBS implantation. Analyses were conducted using the logistf package in R, and results are reported as odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Both non-surgical and selected surgical predictors were statistically analyzed. Predictors were first assessed in univariate models and subsequently in multivariate models, separately for any ICH and symptomatic ICH. All models were adjusted for the number of DBS electrodes implanted to account for the increased risk associated with multiple implantations. Because there were no instances of ICH among patients who underwent staged bilateral implantations, we did not use the type of implantation as a predictor in the regression models. However, we compared patient and procedural characteristics between patients undergoing concurrent or staged bilateral implantations with the Chi-squared test, Wilcoxon rank sum test, and Fisher’s exact test. Statistical significance was defined as p < 0.05. All analyses were performed using R (version 4.5.0). Results Patient demographics We analyzed data from 683 patients who underwent 770 procedures involving the implantation of 1227 DBS leads. The number of males was 425, and the number of females was 258. According to age distribution, 24 patients (3,5%) were children or adolescents up to 18 years old, 429 patients (62,8%) were adults aged 19 to 64 years, and 230 patients (33,7%) were 65 years or older. The mean age at surgery in the entire cohort was 57 years, and the mean duration of neurological symptoms was 12 years to a DBS procedure. PD was the most common indication for DBS. There were 514 patients diagnosed with PD, followed by 92 patients with dystonia. The third common indication was essential tremor diagnosed in 41 patients. Drug-resistant epilepsy was diagnosed in 21 patients, non-essential tremor in 10 patients. Less common indications included 5 patients with neuropsychiatric conditions (3 patients with Tourette syndrome, and 1 patient each with trOCD and TRD (Table 1 ). Taking into account that the majority of patients treated were diagnosed with PD, for statistical reasons, patients with other indications were combined together as non-PD group. The non-PD group included 169 individuals. Hypertension was diagnosed before surgery in 248 patients (36%). Antithrombotic agents were taken by 69 patients (10%) before DBS surgery. Among 683 patients, in 122 (18%) general anesthesia was utilized. Bilateral simultaneous DBS implantations were performed in 454 patients (66%), unilateral implantations in 148 patients (22%), and staged bilateral implantations in 74 patients (11%). Seven patients (1%) underwent more than 2 DBS lead implantation surgeries. Regarding the number of DBS leads implanted in our patients, most of them 528 patients (77%) had 2 DBS leads implanted, followed by 148 patients (22%) with 1 DBS lead implanted. One percent of patients as stated above had more than 2 DBS leads implanted. Among them, 5 patients had 3 DBS leads, and in 2 patients 4 DBS leads were inserted in the course of their movement disorders. A total of 2483 brain penetrations were performed. The mean number of brain penetrations using guiding microelectrodes was 3.64 per patient, 3.22 per procedure, and 2.02 per implanted DBS lead. In total, 1227 DBS leads were implanted, with a mean of 1.80 leads per patient and 1.59 per procedure. Table 1 Patient characteristics Characteristic Overall (N = 683) 1 No ICH (N = 649) 1 ICH(N = 34) 1 Male sex 425 (62%) 401 (62%) 24 (71%) Age at surgery 60 (51, 67) 60 (51, 67) 60 (51, 68) Diagnosis PD 514 (75%) 487 (75%) 27 (79%) Dystonia 92 (13%) 88 (14%) 4 (12%) Essential tremor 41 (6.0%) 39 (6.0%) 2 (5.9%) Drug-resistant epilepsy 21 (3.1%) 20 (3.1%) 1 (2.9%) Tremor SM 5 (0.7%) 5 (0.8%) 0 (0%) Holmes tremor 3 (0.4%) 3 (0.5%) 0 (0%) Tourette syndrome 3 (0.4%) 3 (0.5%) 0 (0%) Cerebellar tremor 1 (0.1%) 1 (0.2%) 0 (0%) OCD, tics 1 (0.1%) 1 (0.2%) 0 (0%) OCD, tics, depression 1 (0.1%) 1 (0.2%) 0 (0%) Poststroke tremor 1 (0.1%) 1 (0.2%) 0 (0%) Duration of symptoms 10 (7, 14) 10 (7, 14) 11 (7, 13) Hypertension 248 (36%) 237 (37%) 11 (32%) Antithrombotic therapy 69 (10%) 60 (9.2%) 9 (26%) Side of implantation Bilateral 454 (66%) 425 (65%) 29 (85%) Unilateral 148 (22%) 144 (22%) 4 (12%) Staged bilateral 74 (11%) 74 (11%) 0 (0%) Mixed 7 (1.0%) 6 (0.9%) 1 (2.9%) Microrecording 346 (51%) 322 (50%) 24 (71%) Bleeding - symptomatic 23 (3.4%) 0 (0%) 23 (68%) Bleeding - permanent symptomatic 6 (0.9%) 0 (0%) 6 (18%) 1 n (%); Median (Q1, Q3) Abbreviation: ICH = Intracranial hemorrhage, OCD = Obsessive-Compulsive Disorder, PD = Parkinson’s disease, SM = Sclerosis Multiplex Overall incidence of ICH Among the 683 patients, 34 (4.98%) experienced ICH, including 6 patients with bilateral ICH. This corresponds to an overall ICH rate of 3.26% (40 events among 1227 DBS leads implantations). Among patients with ICH, hemorrhage was symptomatic in 23 cases (68%), with permanent symptoms observed in 6 patients (18%). Compared to patients without ICH, those with ICH were more often male (71% vs. 62%), whereas age at surgery and symptom duration were similar between groups (Table 1 ). Diagnoses and hypertension rates were also comparable. However, antithrombotic therapy was more frequent among those with ICH (26% vs. 10%). Stereotactic targets aligned with clinical indications: the subthalamic nucleus (STN) was targeted in 72% of cases (885 DBS leads implanted), the globus pallidus internus (GPi) in 16% (201 DBS leads implanted), the ventral intermediate nucleus (VIM) in 4.4% (54 DBS leads implanted), and the anterior nucleus of the thalamus (ANT) in 3.0% (37 DBS leads implanted) (Table 2 ). General anesthesia was used in 240 DBS lead implantations (20%) performed in 122 patients, representing 18% of the entire cohort. MER was applied in 346 patients (51%), corresponding to 687 DBS lead implantations (56%), including 29 hemorrhagic events (73%). Table 2 Implantation characteristics Characteristic Overall (N = 1227) 1 No ICH (N = 1187) 1 ICH(N = 40) 1 Male sex 755 (62%) 727 (61%) 28 (70%) Age at surgery 59 (50, 66) 59 (50, 66) 60 (51, 68) Diagnosis PD 912 (74%) 882 (74%) 30 (75%) Dystonia 184 (15%) 178 (15%) 6 (15%) Essential tremor 66 (5.4%) 63 (5.3%) 3 (7.5%) Drug-resistant epilepsy 40 (3.3%) 39 (3.3%) 1 (2.5%) Tremor SM 8 (0.7%) 8 (0.7%) 0 (0%) Tourette syndrome 6 (0.5%) 6 (0.5%) 0 (0%) Holmes tremor 4 (0.3%) 4 (0.3%) 0 (0%) Cerebellar tremor 2 (0.2%) 2 (0.2%) 0 (0%) OCD, tics 2 (0.2%) 2 (0.2%) 0 (0%) OCD, tics, depression 2 (0.2%) 2 (0.2%) 0 (0%) Poststroke tremor 1 (< 0.1%) 1 (< 0.1%) 0 (0%) Duration of symptoms 10 (7, 14) 10 (7, 13) 11 (7, 15) Stereotactic target STN 885 (72%) 854 (72%) 31 (78%) GPi 201 (16%) 196 (17%) 5 (13%) VIM 54 (4.4%) 53 (4.5%) 1 (2.5%) ANT 37 (3.0%) 36 (3.0%) 1 (2.5%) PSA 37 (3.0%) 35 (2.9%) 2 (5.0%) CM-Spv-Voi 6 (0.5%) 6 (0.5%) 0 (0%) BNST-AC 4 (0.3%) 4 (0.3%) 0 (0%) Vao-Vop 2 (0.2%) 2 (0.2%) 0 (0%) Hippocampus 1 (< 0.1%) 1 (< 0.1%) 0 (0%) Hypertension 429 (35%) 417 (35%) 12 (30%) Antithrombotic therapy 116 (9.5%) 104 (8.8%) 12 (30%) Side of implantation Bilateral 908 (74%) 873 (74%) 35 (88%) Staged bilateral 148 (12%) 148 (12%) 0 (0%) Unilateral 148 (12%) 144 (12%) 4 (10%) Other 23 (1.9%) 22 (1.9%) 1 (2.5%) Microrecording 687 (56%) 658 (55%) 29 (73%) Bleeding - symptomatic 23 (1.9%) 0 (0%) 23 (58%) Bleeding - permanent symptomatic 9 (0.7%) 0 (0%) 9 (23%) 1 n (%); Median (Q1, Q3) Abbreviation: ANT = Anterior Nucleus of the Thalamus, BNST-AC = Bed Nucleus of the Stria Terminalis Anterior Commissure, CM-Spv-Voi = Centromedian Nucleus-Substantia Periventricularis-Nucleus Ventro-oralis Nucleus, GPi = Globus Pallidus Internus, ICH = Intracranial hemorrhage, OCD = Obsessive-Compulsive Disorder, PD = Parkinson’s disease, PSA = Posterior Subthalamic Area, SM = Sclerosis Multiplex, STN = Subthalamic Nucleus, Vao-Vop = ventral oral anterior/posterior nucleus of thalamus, VIM = Ventral Intermediate Nucleus of the Thalamus Non-surgical risk factors related to ICH development Antithrombotic therapy was taken by 69 patients (10%) in the entire cohort. In univariate regression analyses, antithrombotic therapy was the only statistically significant predictor of any ICH (OR = 4.14, p = 0.002). Also in multivariable model, antithrombotic therapy remained a statistically significant predictor of any ICH (OR = 3.75, p = 0.006). Other non-surgical predictors like age at surgery, sex, diagnosis, symptom duration in univariate and also in multivariate analyses were not associated with increased risk of any ICH. Compared to patients without ICH, those with ICH were more often male (71% vs. 62%), whereas age at surgery and symptom duration were similar between groups. Symptomatic ICH was significantly associated with antithrombotic therapy (OR = 4.00, p = 0.010). Also in the multivariate model, only antithrombotic therapy remained a significant predictor (Table 4 ). In symptomatic ICH, sex, diagnosis and duration of symptoms were associated with increased risk of symptomatic ICH but the correlations in univariate and multivariate models were not significant. Table 4 Rare events logistic regression for symptomatic ICH Outcome: symptomatic intracerebral hemorrhage Characteristic 1 Univariate models Multivariable model Odds Ratio 1 95% CI 1 p-value 1 Odds Ratio 1 95% CI 1 p-value 1 Age at surgery 1.01 0.98, 1.05 0.460 1.01 0.98, 1.04 0.562 Male sex 1.73 0.73, 4.67 0.222 1.40 0.68, 3.10 0.369 Antithrombotic therapy 4.00 1.44, 9.96 0.010 4.06 1.62, 9.69 0.003 Hypertension 0.85 0.33, 1.98 0.715 0.67 0.30, 1.45 0.312 MER 2.64 1.06, 7.96 0.037 2.01 0.94, 4.67 0.072 Abbreviation: CI = Confidence Interval, MER = Microelectrode Recording 1 All models adjusted for number of DBS implanted. Surgical risk factors related to ICH development In univariate regression analyses, MER, and the number of brain penetrations performed by microelectrodes were associated with increased ICH risk but did not reach statistical significance (Table 3 ). Symptomatic ICH was significantly associated with MER (OR = 2.64, p = 0.037), and number of brain penetrations (OR = 1.27, p = 0.0019). However, in the multivariate model, there were no surgical predictors for development of symptomatic ICH (Table 4 ). Table 3 Rare events logistic regression for any ICH Outcome: any intracerebral hemorrhage Characteristic 1 Univariate models Multivariable model Odds Ratio 1 95% CI 1 p-value 1 Odds Ratio 1 95% CI 1 p-value 1 Age at surgery 1.01 0.99, 1.04 0.474 1.01 0.98, 1.04 0.562 Male sex 1.50 0.73, 3.29 0.272 1.40 0.68, 3.10 0.369 Antithrombotic therapy 4.14 1.77, 9.02 0.002 4.06 1.62, 9.69 0.003 Hypertension 0.91 0.43, 1.84 0.799 0.67 0.30, 1.45 0.312 MER 1.88 0.90, 4.25 0.092 2.01 0.94, 4.67 0.072 Abbreviation: CI = Confidence Interval, MER = Microelectrode Recording 1 All models adjusted for number of DBS implanted. Among patients with ICH, 29 underwent simultaneous bilateral implantation (ICH rate per lead: 3,9%) and 4 underwent unilateral implantation (ICH rate per lead: 2,7%). There were no instances of ICH among those patients who underwent staged bilateral implantations. Compared to patients who underwent simultaneous bilateral implantations, those who underwent staged procedures were more often male (69% vs. 59%) and older (64 vs. 53 years) and had PD more often (92% vs. 70%). Moreover, in these patients, we used general anesthesia (4,1% vs. 24%) and MER (5,4% vs. 74%) less often; consequently, we performed fewer brain passes per DBS lead implantation (1.07 vs. 2.36). In our investigation, a comprehensive analysis revealed a total of 9 distinct stereotactic targets to treat different neurological or neuropsychiatric diseases. These targets included.: subthalamic nucleus (STN, n = 885), globus pallidus internus (GPI, n = 201), ventral intermediate nucleus (VIM, n = 54), the anterior nucleus of thalamus (ANT, n = 37), posterior subthalamic area (PSA, n = 37), centromedian nucleus substantia periventricularis nucleus ventro-oralis nucleus (CM-Spv-Voi, n = 6), and ventral oral anterior/posterior nucleus of thalamus (VOA/VOP, n = 2), bed nucleus of the stria terminalis anterior commissure (BNST-AC, n = 4), hippocampus (hipp, n = 1). Each stereotactic target corresponded to the implantation of a single electrode, facilitating precise localization within the brain. Configurations of stereotactic targets varied among patients based on the primary disease and predominant symptoms with bilateral interventions presenting not infrequently diverse combinations. Majority of interventions were observed in patients with PD, often featuring a combination of bilateral STN targeting. In the present study, the vast majority of DBS hardware (1173 electrodes; ~96%) was provided by Medtronic. A significantly smaller number of systems were implanted using electrodes from Abbott (n = 30) and Boston Scientific (n = 20). Due to the substantial imbalance in the distribution of hardware across manufacturers, formal statistical comparison was not feasible. However, no statistically significant difference was observed in the incidence of ICH between the three manufacturers, suggesting that the choice of DBS system did not influence the risk of this complication. Risk factor analysis for ICH with transient or permanent neurological deficit. Further, we performed risk factor analysis for ICH with transient and permanent neurological deficit. Due to overall lower rate of permanent neurological deficits found in our patients (6 individuals compromising 0.9% of treated patients) we were unable to find risk factors for ICH producing transient or permanent neurological deficits. We observed that symptomatic ICH with permanent neurological deficits was seen exclusively in PD patients targeting the STN. Discussion Stereotactic functional neurosurgical procedures are relatively safe, with low complication rates of permanent morbidity or mortality. Among these, ICH is among the most severe complications in functional neurosurgery. The incidence of ICH as a complication of DBS lead insertion has been reported to range from 0.5 to 6.9% [ 1 ][ 4 ][ 6 – 9 ]. Despite careful placement of the DBS lead, ICH can occur during or after surgery. Risk factors for ICH can be categorized as patient-specific or surgery-specific. According to the literature, the most convincing patient-specific factors include presence of hypertension, age, and a history of antithrombotic therapy, while surgery-specific factors include trajectory traversing a sulcus or ventricle, as well as the use of intraoperative MER, particularly the number of brain passes made by microelectrodes [ 12 ][ 13 ][ 14 ]. Surgical risks can be reduced with well-planned trajectories using modern neuronavigation. Some of the patient-specific risk factors such as hypertension or antiplatelet therapy may be managed by taking appropriate precautions to lower the incidence of ICH in DBS procedures. Hypertensive patients may benefit from general anesthesia for better blood pressure control. Other patient-specific factors such as age, sex are not modifiable and remain controversial as potential risk factors for ICH. Patient-specific factors have been less extensively studied than surgical ones, and different study groups report contradictory results [ 6 – 8 ][ 10 – 13 ]. In our study, male sex, when compared to patients without ICH, was more frequently associated with ICH, although the difference did not reach statistical significance. Among the 34 patients with ICH, 24 were men (71%). In our cohort of 683 patients, men constituted 62% (425 patients). Yang et al., in a study of 352 PD patients with 686 implanted DBS leads, reported ICH in 11 patients, 10 of whom were men [ 15 ]. According to the authors, the incidence of ICH in men was significantly higher than that in women (p = 0.026). The female to male in Yang’s study (157 women versus 195 men) was similar to as our study cohort [ 15 ]. Santos et al. analyzed risk factors for ICH in 277 patients with a total of 585 implanted DBS leads electrodes [ 16 ]. Besides hypertension, male sex was found to increase the likelihood of hemorrhage (2.2- and 2.7-fold higher risk, respectively), but neither factor reached statistical significance and neither was associated with permanent deficits [ 16 ]. Among the 16 ICH cases, 10 were asymptomatic, and 6 produced transient neurological deficits [ 16 ]. In the recently published study by Holewijn et al., based on one of the largest cohort to date of 800 PD patients treated with DBS, the authors found that male sex was a significant risk factor for symptomatic ICH [ 17 ]. The study cohort included 507 (63%) men and 293 women, with 22 patients (2,8%) experiencing symptomatic ICH. Among the 800 patients, 5 (0.6%) suffered permanent neurological deficits. Interestingly, of these 5 patients, 4 were women and one man [ 17 ]. In our cohort, permanent neurological deficits were observed in 6 patients (0.9%), including 2 women and 4 men. Men were more severely affected, with 1 death, 1 case of permanent hemiplegia, and 2 cases of hemiparesis. In contrast, the 2 women experienced relatively mild dysarthria. Helmers et al. identified male sex as a risk factor for ICH in a large cohort of 485 patients with 970 leads electrodes implanted [ 18 ]. In contrast, several authors did not find the male sex or sex in general to be significant risk factor for ICH following DBS procedures [ 10 ][ 11 ][ 13 ][ 19 ]. Some studies have suggested that the combination of male sex and hypertension may constitute an enhanced risk for ICH [ 10 ][ 15 ]. Among all the patient-related risk factors examined, hypertension appears to shows one the most consistent association with ICH in DBS [ 11 ][ 14 ][ 20 ]. Hypertension has also been reported as a risk factor in earlier studies evaluating the cumulative experience not only in DBS procedures, but also in ablative functional procedures [ 7 – 11 ]. Xiaowu et al. examined risk factors in a large cohort of 644 patients who underwent lesioning, DBS or both procedures [ 11 ]. The incidence of ICH was 2.5 times higher in hypertensive patients (p < 0.05) compared in normotensive patients. Gorgulho et al. and Elias et al. also found that hypertension was a significant risk factor for ICH [ 8 ][ 20 ]. Several other studies have confirmed that hypertension is an important factor in the development of ICH in functional procedures [ 6 ][ 11 ][ 12 ][ 21 ]. It should be noted that the definition of hypertension varied across studies. Gorgulho et al. defined hypertension as occurring when intraoperative or postoperative systolic blood pressure (BP) reached 160 mmHg or higher [ 20 ]. Sansur et al. classified patients as hypertensive if the diagnosis was documented in the medical record or if patients had a history of antihypertensive treatment [ 14 ]. In the present study, we defined hypertension as a preexisting diagnosis in patients who were taking antihypertensive medication at the time of admission. Among our cohort of 683 patients, 248 (36%) were diagnosed with hypertension; however, the incidence of ICH was similar between hypertensive and normotensive patients. We paid special attention not merely to history of hypertension per se, but to actual blood pressure values during surgery and in the early postoperative period. During DBS procedures, the anesthesiologist maintained intraoperative BP below 130/80 mmHg, and below 140/90 mmHg in the first 24 hours after surgery. In the study, six procedures were aborted due to uncontrolled high BP. These patients were operated on at a later date, mostly under general anesthesia, without hemorrhagic complications. Intraoperative bleeding caused by elevated systolic BP may lead to neurological deficits with altered consciousness and is readily identified on emergency intraprocedural CT. This type of hemorrhage is usually associated with permanent neurological deficits. Shin et al. identified intraoperative SBP as a risk factor for all cases of ICH which resulted in permanent neurological deficits. In their analysis, systolic BP values were evaluated in detail, and a threshold of 129.4 mmHg was identified as the cut-off for the occurrence of ICH [ 21 ]. Moreover, systolic BP greater than 148.3 mmHg was associated with ICH leading to permanent neurological deficits [ 21 ]. Several large-cohort studies also identified male sex and hypertension as key risk factors [ 15 – 17 ][ 22 ][ 23 ]. Interestingly, most of these studies associate these two patient-specific risk factors primarily with advanced Parkinson’s disease [ 15 – 17 ]. However, some studies have found no significant association between hypertension and ICH [ 17 ][ 24 ]. Besides sex and hypertension, age is also regarded as a possible risk factor for ICH. In our cohort, we did not identify age as a predisposing factor for ICH. There was no difference in the incidence of ICH between patients aged 65 years or younger and those older than 65. Our results regarding age at the time of surgery as a risk factors have been confirmed by other studies [ 7 ][ 10 ][ 11 ]. Holewijn et al. did not mention age at surgery as a risk factor for either symptomatic or asymptomatic ICH in PD patients undergoing DBS [ 17 ]. In contrast, several authors have reported that age at surgery plays an important role in incidence of ICH following DBS. Sansur et al. found that in a group of 259 patients, age was significantly associated with ICH, with the mean age of patients with symptomatic ICH being 65 years compared to 41 years in those without ICH [ 14 ]. Patient age at the time of surgery as a risk factor for ICH was also emphasized by Ben-Haim et al., who reported a mean age of 64.2 ± 9.5 years in patients with ICH versus 53.3 ± 15.9 years in those without [ 13 ]. Similarly, Martin et al. found that older age was a statistically significant risk factor, with the average age of patients with ICH being 64.8 years compared to 57.9 years in the overall cohort (p = 0.0125) [ 25 ]. In our study, antithrombotic therapy was used by 69 patients (10%) and was the only statistically significant predictor of ICH in both univariable and multivariable models. In all cases, antithrombotic agents were discontinued at least 10 days prior to the planned DBS procedure. In contrast, Shin et al. also discontinued antithrombotic therapy 10 days before DBS but did not observe an increased risk of ICH [ 21 ]. Similarly, Sansur et al. reported no increased hemorrhagic risk among 23 of 143 patients (16%) with prior antithrombotic use [ 14 ]. Besides the patient-specific risk factors for ICH discussed above, the underlying diagnosis and the anatomical target chosen for DBS may also represent potential risk factors. For statistical purposes, our patient cohort was divided into two groups based on diagnosis: patients with Parkinson’s disease (PD group) and patients with other indications (non-PD group), due to diagnostic heterogeneity and the small sample sizes of other disorders. We were unable to identify a higher incidence of ICH between these two groups. Some authors have reported that the diagnosis of PD is associated with a higher risk of ICH compared to patients with dystonia or essential tremor [ 6 ][ 14 ]. Sansur et al. found that a diagnosis of PD was associated with an increased risk of ICH [ 14 ]. Elias et al. also reported a threefold higher ICH rate in PD vs. dystonia or ET (8% vs. 2.5%), though not statistically significant [ 8 ]. Age differences between diagnostic groups may partly explain this variability. Other authors have likewise concluded that the underlying neurological diagnosis does not influence the risk of ICH in patients undergoing DBS [ 7 ][ 13 ]. Based on our experience, we did not find a significant association between diagnosis and overall ICH incidence. Different diagnoses are treated using different anatomical targets for DBS. Patients with PD are typically treated by implanting DBS electrodes into the STN, depending on clinical symptoms, or less frequently into the GPi. In tremor-dominant PD, the PSA may also be used. In patients with dystonia, the targets include the GPi or, less commonly, the STN. Essential tremor is usually treated with DBS targeting the Vim or the PSA. To determine whether a particular anatomical target carries a higher risk of ICH, such a study would need to be conducted in a homogeneous group of patients with the same diagnosis. In our cohort, we were unable to correlate any specific anatomical target with an increased risk of overall ICH. However, as mentioned earlier, symptomatic ICH with permanent neurological deficits occurred exclusively in PD patients. Other studies have also failed to find significant differences in ICH risk based on anatomical target [ 11 ][ 14 ]. Binder et al. reported that the GPi target may be more vulnerable to ICH due to the presence of lenticulostriate vessels in the target area, compared with the STN [ 7 ]. Another potential source of bleeding during GPi targeting is injury to vessels in the cisternal space around the optic tract, caused by microelectrodes or macroelectrodes [ 26 ]. The burr holes used for GPi targeting are generally placed more posteriorly. Bridging veins may be injured during burr hole drilling or dural opening, potentially leading to delayed venous infarction. Such complications have been described in the literature [ 27 ]. Despite the above-mentioned risks, some authors consider GPi targeting to be safer than STN [ 21 ]. The trajectory to the GPi is shorter than that to the STN, as the STN lies deeper within the brain. A shorter intracerebral path may reduce the risk of bleeding. ICH occurring during GPi targeting typically affects the basal ganglia, whereas STN targeting may lead to hemorrhage in the thalamus or mesencephalon. STN-related ICH is more often associated with permanent neurological deficits and can be fatal [ 21 ]. In our series, all cases of permanent neurological deficits due to ICH occurred in PD patients who were targeted at the STN, including one death. Our findings may suggest that STN targeting is associated with a higher risk of ICH resulting in permanent neurological deficits compared to GPi (although this could not be confirmed statistically). Other authors have reported that while the overall incidence of ICH between STN and GPi targets is similar, permanent neurological deficits are more frequently observed with STN targeting in PD patients [ 21 ]. Sorer et al. did not find any patient-specific risk factors, including sex, age, diagnosis, anatomical target, or device manufacturer, to be associated with an increased incidence of complications, including ICH [ 28 ]. In contrast, surgical experience was found to be significantly associated with complication rates (p < 0.001) [ 28 ]. Other studies have also concluded that the experience of the surgical team plays a crucial role in reducing the overall rate of DBS-related complications, including ICH [ 4 , 17 , 19 ]. We support this conclusion, as we observed no permanent neurological deficits due to ICH in our last 350 patients. There are some limitations in our study. Our 17-year retrospective period encompassed some changes in surgical technique and imaging protocols. The strict scheduled intraprocedural stereotactic CT was introduced from January 2018 and before this period postoperative CT was done at various time intervals after DBS. Consequently, some silent hemorrhages may have gone undetected in our earlier years spanning period from 2008 to 2017. Due to the relatively small number of hemorrhagic events in our cohort, particularly those resulting in permanent neurological deficits (6 patients out of 683), we were unable to perform certain statistical analyses that could be generalized to the broader population. This limitation is common among studies investigating rare adverse events. To increase statistical robustness for selected features, we grouped relevant variables where appropriate, such as combining diagnoses into PD and non-PD categories. In cases where statistical analysis was not feasible, descriptive reporting was used. As a result, some of the associations observed in this study should be interpreted with caution. Conclusions DBS procedures demonstrate an overall favorable safety profile, with an ICH prevalence of approximately 4.98% and a low incidence of permanent neurological deficits, affecting only 0.9% of treated patients. Our analysis revealed a statistically significant association between certain patient-specific risk factors and ICH, indicating that preoperative antithrombotic therapy remained a significant predictor of hemorrhagic complications. Other non-surgical and surgical risk factors analyzed including sex, age at surgery, diagnosis, symptom duration, presence of hypertension, use of MER, number of guiding microelectrodes utilized, and type of anesthesia, were not identified as predictors of overall ICH. Although the diagnosis of PD and targeting of the STN were observed exclusively in patients who developed permanent neurological deficits, these factors were not statistically significant in relation to the overall ICH rate in the present analysis. Strict intraprocedural and scheduled postoperative CT or MRI may help detect a greater number of asymptomatic ICH cases. The risk of ICH appears to be influenced by a combination of factors, which can be grouped into three categories: patient-specific factors, surgery-specific factors, and the experience of the surgical team. Further studies are needed to better determine the true incidence of ICH, with particular emphasis on reducing events that result in permanent neurological deficits. Declarations Author contributions Karol Karamon: Conceptualization, Methodology, Formal analysis, Investigation, Data curation, Writing - Original Draft, Visualization Michał Sobstyl: Methodology, Validation, Investigation, Resources, Writing - Review & Editing, Supervision, Project administration Łukasz Smoliński: Methodology, Formal analysis, Writing - Review & Editing, Visualization Funding No financial support was received for the conduct of this research. Availability of data and materials All data relevant to this study are included in the manuscript, including summarized results presented in tables. Due to institutional and ethical restrictions related to patient confidentiality, the raw datasets are not publicly available. Additional information may be obtained from the corresponding author upon reasonable request. Ethics approval and consent to participate This retrospective study involved analysis of anonymized clinical data collected as part of routine care. According to institutional and national regulations, ethical committee approval and informed consent were not required. Competing interests The authors declare no conflict of interest Clinical trial Clinical trial number: not applicable. References Hariz M, Blomstedt P (2022) Deep brain stimulation for Parkinson's disease. J Intern Med 292(5):764–778. 10.1111/joim.13541 Najera RA, Mahavadi AK, Khan AU, Boddeti U, Del Bene VA, Walker HC, Bentley JN (2023) eCollection. Alternative patterns of deep brain stimulation in neurologic and neuropsychiatric disorders. Front Neuroinform 2023 Jun 21:17:1156818. 10.3389/fninf.2023.1156818 Gouveia FV, Warsi NM, Suresh H, Matin R, Ibrahim GM (2024) Neurostimulation treatments for epilepsy: Deep brain stimulation, responsive neurostimulation and vagus nerve stimulation. Neurotherapeutics 21(3):e00308. 10.1016/j.neurot.2023.e00308 Epub 2024 Jan 4 Falowski SM, Ooi YC, Bakay RA (2015) Long-Term Evaluation of Changes in Operative Technique and Hardware-Related Complications With Deep Brain Stimulation. Neuromodulation 18(8):670–677. 10.1111/ner.12335 Runge J, Nagel JM, Cassini Ascencao L et al (2022) Are Transventricular Approaches Associated With Increased Hemorrhage? A Comparative Study in a Series of 624 Deep Brain Stimulation Surgeries. Oper Neurosurg 23(2):e108–e113. 10.1227/ons.0000000000000275 Zrinzo L, Foltynie T, Limousin P, Hariz MI (2012) Reducing hemorrhagic complications in functional neurosurgery: a large case series and systematic literature review. J Neurosurg 116(1):84–94. 10.3171/2011.8.JNS101407 Binder DK, Rau GM, Starr PA (2005) Risk factors for hemorrhage during microelectrode-guided deep brain stimulator implantation for movement disorders. Neurosurgery. ;56(4):722 – 32; discussion 722 – 32. 10.1227/01.neu.0000156473.57196.7e 15792511 Elias WJ, Sansur CA, Frysinger RC (2009) Sulcal and ventricular trajectories in stereotactic surgery. J Neurosurg 110(2):201–207. 10.3171/2008.7.17625 Runge J, Nagel JM, Schrader C et al (2023) Microelectrode recording and hemorrhage in functional neurosurgery: a comparative analysis in a consecutive series of 645 procedures. J Neurosurg 140(5):1442–1450 Published 2023 Nov 3. 10.3171/2023.8.JNS23613 Seijo F, Alvarez de Eulate Beramendi S, Santamarta Liébana E et al (2014) Surgical adverse events of deep brain stimulation in the subthalamic nucleus of patients with Parkinson's disease. The learning curve and the pitfalls. Acta Neurochir (Wien) 156(8):1505–1512. 10.1007/s00701-014-2082-0 Xiaowu H, Xiufeng J, Xiaoping Z et al (2010) Risks of intracranial hemorrhage in patients with Parkinson's disease receiving deep brain stimulation and ablation. Parkinsonism Relat Disord 16(2):96–100. 10.1016/j.parkreldis.2009.07.013 Frey J, Cagle J, Johnson KA et al (2022) Past, Present, and Future of Deep Brain Stimulation: Hardware, Software, Imaging, Physiology and Novel Approaches. Front Neurol . ;13:825178. Published 2022 Mar 9. 10.3389/fneur.2022.825178 Ben-Haim S, Asaad WF, Gale JT, Eskandar EN (2009) Risk factors for hemorrhage during microelectrode-guided deep brain stimulation and the introduction of an improved microelectrode design. Neurosurgery 64(4):754–763. 10.1227/01.NEU.0000339173.77240.34 Sansur CA, Frysinger RC, Pouratian N et al (2007) Incidence of symptomatic hemorrhage after stereotactic electrode placement. J Neurosurg 107(5):998–1003. 10.3171/JNS-07/11/0998 Yang C, Qiu Y, Wang J, Wu Y, Hu X, Xi Wu X (2020) Intracranial hemorrhage risk factors of deep brain stimulation for Parkinson's disease: a 2-year follow-up study. J Int Med Res 48(5):300060519856747. 10.1177/0300060519856747 Santos B, Rui Vaz AC, Braga M, Rito D, Lucas, Clara Chamadoira. Intracerebral hemorrhage after deep brain stimulation surgery guided with microelectrode recording: analysis of 297 procedures. Neurocirugia (Engl Ed) 2024 Mar-Apr;35(2):79–86. 10.1016/j.neucie.2023.09.001 Holewijn RA, Yarit Wiggerts M, Bot D, Verbaan, Rob MA, de Bie R, Schuurman (2024) Pepijn van den Munckhof. Surgical Complications in Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease: Experience in 800 Patients. Stereotact Funct Neurosurg 102(5):275–283. 10.1159/000539483 Helmers AK, Kubelt C, Birkenfeld F et al (2020) Screening for Platelet Dysfunction and Use of Prophylactic Tranexamic Acid in Patients Undergoing Deep Brain Stimulation: A Retrospective Analysis of Incidence and Outcome of Intracranial Hemorrhage. Stereotact Funct Neurosurg 98(3):176–181. 10.1159/000505714 Doshi PK, Rai N, Das D (2022) Surgical and Hardware Complications of Deep Brain Stimulation-A Single Surgeon Experience of 519 Cases Over 20 Years. Neuromodulation 25(6):895–903. 10.1111/ner.13360 Gorgulho A, De Salles AA, Frighetto L, Behnke E (2005) Incidence of hemorrhage associated with electrophysiological studies performed using macroelectrodes and microelectrodes in functional neurosurgery. J Neurosurg 102(5):888–896. 10.3171/jns.2005.102.5.0888 Shin HK, Kim MS, Yoon HH, Chung SJ, Jeon SR (2022) The risk factors of intracerebral hemorrhage in deep brain stimulation: does target matter? Acta Neurochir (Wien) 164(2):587–598. 10.1007/s00701-021-04977-y Farrokh R, Farrokhi MT, Marsans M, Sikora SE, Monsell AK, Wright Meghan Palmer, Aiden Hoefer, Pam McLeod, Jamie Mark, Jonathan Carlson. Pre-operative smoking history increases risk of infection in deep brain stimulation surgery. J Clin Neurosci 2019 Nov :69:88–92. doi: 10.1016/j.jocn.2019.08.026. Epub 2019 Aug 21. Sobstyl M, Aleksandrowicz M, Ząbek M, Pasterski T (2019) Hemorrhagic complications seen on immediate intraprocedural stereotactic computed tomography imaging during deep brain stimulation implantation. J Neurol Sci 400:97–103. 10.1016/j.jns.2019.01.033 Cordeiro JG, Diaz A, Davis JK, Luca DGD, Farooq G, Luca CC Jonathan Russell Jagid. Safety of Noncontrast Imaging-Guided Deep Brain Stimulation Electrode Placement in Parkinson Disease. World Neurosurg 2020 Feb :134:e1008–e1014. 10.1016/j.wneu.2019.11.071 Martin AJ, Starr PA, Ostrem JL (2017) Larson. Hemorrhage Detection and Incidence during Magnetic Resonance-Guided Deep Brain Stimulator Implantations. Stereotact Funct Neurosurg 95(5):307–314. 10.1159/000479287 Damier P, Thobois S, Witjas T et al (2007) Bilateral deep brain stimulation of the globus pallidus to treat tardive dyskinesia. Arch Gen Psychiatry 64(2):170–176. 10.1001/archpsyc.64.2.170 Sobstyl M, Brzuszkiewicz-Kuźmicka G, Aleksandrowicz M, Pasterski T (2019) Large Hemorrhagic Cerebral Venous Infarction due to Deep Brain Stimulation Leads Placement. Report of 2 Cases. Turk Neurosurg 29(4):611–614. 10.5137/1019-5149.JTN.22281-17.3 Sorar M, Hanalioglu S, Kocer B, Eser MT, Comoglu SS, Kertmen H (2018) Experience Reduces Surgical and Hardware-Related Complications of Deep Brain Stimulation Surgery: A Single-Center Study of 181 Patients Operated in Six Years. Parkinsons Dis . ;2018:3056018. Published 2018 Jul 22. 10.1155/2018/3056018 Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8575448","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":583675825,"identity":"2273f42f-8cd2-409d-a550-126fc6d548a5","order_by":0,"name":"Karol Sylwester Karamon","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA80lEQVRIiWNgGAWjYBACCRDxgCEByq0AYmbmBsJaEuBazoC0MJKihbENTOLXItl+9uGDBIY0efP204mPC+fVRvO3A7X8qNiGU4s0T7qxQQJDjuGcM7mbjWduO5474zBjA2PPmds4tcgxpLFJJDBUMM5gyN0mzbvtWG4DUAszYxseLfzPwFrsZ/C/BWqZcyx3PiEt0hJgW3ISZ0iAbGmoyd1ASIvkjGfMBgkGackzJN5uNuY5diB3I1DLQXx+kTifxvjgQ0Wy7Qz+3I2PeWrqcuedP3zwwY8K3FogwADOOgwmDxBQjwLqSFE8CkbBKBgFIwQAAIFrVa2ScPqdAAAAAElFTkSuQmCC","orcid":"","institution":"Institute of Psychiatry and Neurology","correspondingAuthor":true,"prefix":"","firstName":"Karol","middleName":"Sylwester","lastName":"Karamon","suffix":""},{"id":583675826,"identity":"02e31604-c8f0-4c63-88ed-fdaca80a115b","order_by":1,"name":"Michał Sobstyl","email":"","orcid":"","institution":"Institute of Psychiatry and Neurology","correspondingAuthor":false,"prefix":"","firstName":"Michał","middleName":"","lastName":"Sobstyl","suffix":""},{"id":583675827,"identity":"28505abf-e4e7-423e-9a9c-7196a615bb70","order_by":2,"name":"Łukasz Smoliński","email":"","orcid":"","institution":"unaffilated","correspondingAuthor":false,"prefix":"","firstName":"Łukasz","middleName":"","lastName":"Smoliński","suffix":""}],"badges":[],"createdAt":"2026-01-11 19:23:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8575448/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8575448/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s10143-026-04226-9","type":"published","date":"2026-04-15T15:58:09+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":107350787,"identity":"c1f67f03-4568-462b-884e-cc1d0909c4fa","added_by":"auto","created_at":"2026-04-20 16:04:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":657878,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8575448/v1/db07deea-bbbf-4ffd-a6cc-8f1f12361063.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Hemorrhagic complications in deep brain stimulation: analysis of non-surgical risk factors in a cohort of 683 patients","fulltext":[{"header":"Introduction","content":"\u003cp\u003eDeep brain stimulation (DBS) is a neurosurgical treatment method used to treat a spectrum of movement disorders, including Parkinson\u0026rsquo;s disease (PD), essential tremor (ET), and dystonia [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Additionally, DBS has proven effective in treating drug-resistant epilepsy (DRE) and neuropsychiatric disorders such as treatment-resistant obsessive-compulsive disorder (trOCD), treatment-resistant depression (TRD) and Tourette syndrome [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The procedure involves the precise implantation of DBS leads into deep brain nuclei using a stereotactic technique. The implantation is performed after placement of a stereotactic ring on the patient\u0026rsquo;s head, typically under local or general anesthesia [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Subsequently, using a neuronavigation system, the safest stereotactic trajectories from the brain surface to the target nuclei are planned, avoiding cerebral blood vessels, sulci, and ventricles [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Accurate placement of the DBS leads at the intended neurophysiological-neuroanatomical target is crucial for achieving optimal clinical outcomes.\u003c/p\u003e \u003cp\u003eThe implantation of DBS leads is inevitably associated with a risk of intracranial hemorrhage (ICH) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Many publications have focused on surgical strategies and risk factors associated with minimizing the risk of ICH during DBS implantation. [\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Less attention has been paid to non-surgical factors contributing to the development of ICH [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. These factors include indication and duration of illness for DBS treatment as well as patients specific variables such as age at surgery, sex, presence of hypertension, and history of antithrombotics including antiplatelet or anticoagulant therapy [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe primary objective of the current study was to assess the prevalence of ICH and identify non-surgical risk factors for its development based on demographic and clinical data, including their evaluation in the overall patient population as well as in subgroups with symptomatic and asymptomatic ICH. In addition, selected surgical risk factors identified during the study are also presented.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003eThe study design involves a retrospective analysis of all 683 consecutive patients who underwent DBS surgery for movement disorders, neuropsychiatric disorders and drug-resistant epilepsy at the Department of Neurosurgery, Institute of Psychiatry and Neurology in Warsaw, Poland, from November 2008 to April 2025.\u003c/p\u003e \u003cp\u003eWithin the Institute of Psychiatry and Neurology, the regulations oblige researchers to regularly report all the complications of DBS procedures (Ethical Committee approval of Institute of Psychiatry and Neurology number 26/2023). The approval for reporting (publishing) all of the complications related to DBS procedures including ICH is valid for three years from the date of issuance. The necessity for acquiring additional written informed consent from the patients or their family members/caregivers was not required, given the retrospective nature of the study and the anonymization of personal data.\u003c/p\u003e \u003cp\u003eThe medical records of patients were reviewed, and data were collected using a standardized protocol. Data collected included demographic and clinical factors such as diagnosis, duration of symptoms, age at operation, gender, presence of hypertension and recent history of antiplatelet or anticoagulant therapy. Antiplatelet therapy included aspirin and/or P2Y12 receptor inhibitors, whereas anticoagulant therapy included vitamin K antagonists and direct oral anticoagulants. Together, these medications were classified as antithrombotic agents, all of which were discontinued at least 10 days prior to the planned DBS procedure in accordance with institutional perioperative protocols. In addition, surgical variables were also recorded, including the use of microelectrode recording (MER) and number of guiding electrodes utilized, type of implantation (bilateral simultaneous, bilateral staged, unilateral, or mixed), targeted stereotactic structure, type of anesthesia (general or local), and the manufacturer brand of the implanted system. We have analyzed only de novo DBS procedures. All reimplantation procedures due to DBS lead brakeage and DBS lead/s removal due to infection were excluded.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSurgical DBS procedures\u003c/h3\u003e\n\u003cp\u003eFor patients with PD, ET and other forms of non-ET movement disorders, a Leksell series G stereotactic frame was applied under local anesthesia, while general anesthesia was used for the patients with dystonia, neuropsychiatric disorders, Tourette syndrome or DRE. T2-weighted and T1-weighted 3D volumetric contrast-enhanced MRI scans were acquired on either a 1.5 Tesla or 3 Tesla magnet (Signa MRI Imaging Scanner, General Electric). Stereotactic G or Vantage frame (Elekta, Instruments, Stockholm, Sweden) were used. Following local/general anesthesia, the stereotactic head frame was secured to the patient\u0026rsquo;s skull, and contrast-enhanced CT scans with a slice thickness of 1.25 mm were obtained. These CT and MRI images were then transferred to surgical planning software; Brainlab (Brainlab iPlan 3.0.6, AG, Munich, Germany) or (Framelink S8, StealthStation, Medtronic, Minneapolis, MN, USA). The anesthesiologist kept intraoperative blood pressures below 130/80 mmHg during DBS procedures and \u0026lt;\u0026thinsp;140/90 mmHg after the surgery. The burr hole was typically placed 3.5 to 5 cm lateral to the midline in close proximity to or at the coronal suture level, targeting vessel-free surface of the frontal gyrus. The lead anchoring system at the burr hole was used in all patients (from different manufactures Medtronic, Bostonsientific less frequently Abbott). The dura was coagulated and sharply opened only at the point of stereotactic trajectory. In MER-guided procedures, usually three microelectrodes per hemisphere were inserted with the aid of the microdrive attached to the Leksell stereotactic arc. The 4-channel Lead point system (Medtronic) was used in MER-based procedures. Macrostimulation was subsequently performed using the dedicated macro tip constituting an integral part of the used microelectrode. Following determination of the clinically most optimal stimulation spot, the microelectrodes were withdrawn and the permanent DBS lead(s) were implanted. In non-MER-based DBS procedures, one guiding MER cannula (FHC, United States) was introduced to the stereotactic target. The depth of the guiding cannula was checked by lateral fluoroscopy. Thereafter, the guiding MER cannula was replaced by permanent DBS electrode which was introduced to the stereotactic target under lateral fluoroscopic guidance. Bipolar or monopolar stimulation were done through the quadripolar DBS lead using the external clinician Medtronic programmer. The implantable pulse generators (IPGs) were implanted in general anesthesia during the same operative session.\u003c/p\u003e\n\u003ch3\u003ePostoperative Imaging and ICH assessment\u003c/h3\u003e\n\u003cp\u003eAll patients underwent postoperative CT examination following DBS procedures. Between November 2008 and December 2017, postoperative CT scans were obtained predominantly within the first 24 hours after surgery, with the majority performed within the first 12 hours. From January 2018 onward, CT imaging was performed intraoperatively with the stereotactic Leksell G or Vantage head frames in place, and delayed postoperative CT was not routinely performed unless clinically indicated. The location of each intracranial hemorrhage and its temporal relationship to the implantation procedure were recorded in all cases. Hemorrhages were classified as either asymptomatic or symptomatic. Asymptomatic hemorrhages produced no neurological symptoms. Symptomatic hemorrhages were further categorized as \u0026ldquo;transient\u0026rdquo; and defined as transient and mild symptoms lasting fewer than seven days or \u0026ldquo;permanent\u0026rdquo; involving permanent or long-lasting neurological deficits or mental status changes persisting for more than seven days.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eDescriptive statistics, including means with standard deviations (SD) for continuous variables and counts with percentages for categorical variables, were used to summarize patient and procedural characteristics. To examine the association between ICH and selected clinical and surgical predictors, we applied Firth\u0026rsquo;s penalized likelihood logistic regression. This method reduces bias in analyses involving rare events, such as ICH following DBS implantation. Analyses were conducted using the logistf package in R, and results are reported as odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Both non-surgical and selected surgical predictors were statistically analyzed. Predictors were first assessed in univariate models and subsequently in multivariate models, separately for any ICH and symptomatic ICH. All models were adjusted for the number of DBS electrodes implanted to account for the increased risk associated with multiple implantations. Because there were no instances of ICH among patients who underwent staged bilateral implantations, we did not use the type of implantation as a predictor in the regression models. However, we compared patient and procedural characteristics between patients undergoing concurrent or staged bilateral implantations with the Chi-squared test, Wilcoxon rank sum test, and Fisher\u0026rsquo;s exact test. Statistical significance was defined as p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. All analyses were performed using R (version 4.5.0).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePatient demographics\u003c/h2\u003e \u003cp\u003eWe analyzed data from 683 patients who underwent 770 procedures involving the implantation of 1227 DBS leads. The number of males was 425, and the number of females was 258. According to age distribution, 24 patients (3,5%) were children or adolescents up to 18 years old, 429 patients (62,8%) were adults aged 19 to 64 years, and 230 patients (33,7%) were 65 years or older. The mean age at surgery in the entire cohort was 57 years, and the mean duration of neurological symptoms was 12 years to a DBS procedure. PD was the most common indication for DBS. There were 514 patients diagnosed with PD, followed by 92 patients with dystonia. The third common indication was essential tremor diagnosed in 41 patients. Drug-resistant epilepsy was diagnosed in 21 patients, non-essential tremor in 10 patients. Less common indications included 5 patients with neuropsychiatric conditions (3 patients with Tourette syndrome, and 1 patient each with trOCD and TRD (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Taking into account that the majority of patients treated were diagnosed with PD, for statistical reasons, patients with other indications were combined together as non-PD group. The non-PD group included 169 individuals. Hypertension was diagnosed before surgery in 248 patients (36%). Antithrombotic agents were taken by 69 patients (10%) before DBS surgery. Among 683 patients, in 122 (18%) general anesthesia was utilized. Bilateral simultaneous DBS implantations were performed in 454 patients (66%), unilateral implantations in 148 patients (22%), and staged bilateral implantations in 74 patients (11%). Seven patients (1%) underwent more than 2 DBS lead implantation surgeries. Regarding the number of DBS leads implanted in our patients, most of them 528 patients (77%) had 2 DBS leads implanted, followed by 148 patients (22%) with 1 DBS lead implanted. One percent of patients as stated above had more than 2 DBS leads implanted. Among them, 5 patients had 3 DBS leads, and in 2 patients 4 DBS leads were inserted in the course of their movement disorders. A total of 2483 brain penetrations were performed. The mean number of brain penetrations using guiding microelectrodes was 3.64 per patient, 3.22 per procedure, and 2.02 per implanted DBS lead. In total, 1227 DBS leads were implanted, with a mean of 1.80 leads per patient and 1.59 per procedure.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOverall (N\u0026thinsp;=\u0026thinsp;683)\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo ICH (N\u0026thinsp;=\u0026thinsp;649)\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eICH(N\u0026thinsp;=\u0026thinsp;34)\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale sex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e425 (62%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e401 (62%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24 (71%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60 (51, 67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60 (51, 67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e60 (51, 68)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiagnosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e514 (75%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e487 (75%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27 (79%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDystonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e92 (13%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e88 (14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (12%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEssential tremor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41 (6.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39 (6.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (5.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDrug-resistant epilepsy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (3.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (3.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (2.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTremor SM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (0.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (0.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHolmes tremor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (0.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (0.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTourette syndrome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (0.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (0.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebellar tremor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOCD, tics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOCD, tics, depression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePoststroke tremor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (7, 14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (7, 14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (7, 13)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e248 (36%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e237 (37%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (32%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntithrombotic therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69 (10%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60 (9.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (26%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSide of implantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilateral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e454 (66%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e425 (65%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29 (85%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnilateral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e148 (22%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e144 (22%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (12%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStaged bilateral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74 (11%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74 (11%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMixed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (1.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (0.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (2.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMicrorecording\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e346 (51%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e322 (50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24 (71%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBleeding - symptomatic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23 (68%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBleeding - permanent symptomatic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (0.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (18%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u0026nbsp;n (%); Median (Q1, Q3)\u003c/p\u003e \u003cp\u003eAbbreviation: ICH\u0026thinsp;=\u0026thinsp;Intracranial hemorrhage, OCD\u0026thinsp;=\u0026thinsp;Obsessive-Compulsive Disorder, PD\u0026thinsp;=\u0026thinsp;Parkinson\u0026rsquo;s disease, SM\u0026thinsp;=\u0026thinsp;Sclerosis Multiplex\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eOverall incidence of ICH\u003c/h3\u003e\n\u003cp\u003eAmong the 683 patients, 34 (4.98%) experienced ICH, including 6 patients with bilateral ICH. This corresponds to an overall ICH rate of 3.26% (40 events among 1227 DBS leads implantations). Among patients with ICH, hemorrhage was symptomatic in 23 cases (68%), with permanent symptoms observed in 6 patients (18%). Compared to patients without ICH, those with ICH were more often male (71% vs. 62%), whereas age at surgery and symptom duration were similar between groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Diagnoses and hypertension rates were also comparable. However, antithrombotic therapy was more frequent among those with ICH (26% vs. 10%).\u003c/p\u003e \u003cp\u003eStereotactic targets aligned with clinical indications: the subthalamic nucleus (STN) was targeted in 72% of cases (885 DBS leads implanted), the globus pallidus internus (GPi) in 16% (201 DBS leads implanted), the ventral intermediate nucleus (VIM) in 4.4% (54 DBS leads implanted), and the anterior nucleus of the thalamus (ANT) in 3.0% (37 DBS leads implanted) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). General anesthesia was used in 240 DBS lead implantations (20%) performed in 122 patients, representing 18% of the entire cohort. MER was applied in 346 patients (51%), corresponding to 687 DBS lead implantations (56%), including 29 hemorrhagic events (73%).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eImplantation characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOverall (N\u0026thinsp;=\u0026thinsp;1227)\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo ICH (N\u0026thinsp;=\u0026thinsp;1187)\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eICH(N\u0026thinsp;=\u0026thinsp;40)\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale sex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e755 (62%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e727 (61%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28 (70%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59 (50, 66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59 (50, 66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e60 (51, 68)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiagnosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e912 (74%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e882 (74%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30 (75%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDystonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e184 (15%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e178 (15%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (15%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEssential tremor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66 (5.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63 (5.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (7.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDrug-resistant epilepsy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40 (3.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39 (3.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (2.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTremor SM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (0.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (0.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTourette syndrome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (0.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (0.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHolmes tremor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (0.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (0.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebellar tremor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (0.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (0.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOCD, tics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (0.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (0.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOCD, tics, depression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (0.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (0.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePoststroke tremor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (\u0026lt;\u0026thinsp;0.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (\u0026lt;\u0026thinsp;0.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (7, 14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (7, 13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (7, 15)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStereotactic target\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSTN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e885 (72%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e854 (72%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31 (78%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGPi\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e201 (16%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e196 (17%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (13%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVIM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54 (4.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53 (4.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (2.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eANT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37 (3.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36 (3.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (2.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37 (3.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35 (2.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (5.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCM-Spv-Voi\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (0.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (0.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBNST-AC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (0.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (0.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVao-Vop\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (0.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (0.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHippocampus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (\u0026lt;\u0026thinsp;0.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (\u0026lt;\u0026thinsp;0.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e429 (35%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e417 (35%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (30%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntithrombotic therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e116 (9.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e104 (8.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (30%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSide of implantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilateral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e908 (74%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e873 (74%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35 (88%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStaged bilateral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e148 (12%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e148 (12%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnilateral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e148 (12%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e144 (12%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (10%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (1.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (1.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (2.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMicrorecording\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e687 (56%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e658 (55%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29 (73%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBleeding - symptomatic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (1.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23 (58%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBleeding - permanent symptomatic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (0.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (23%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u0026nbsp;n (%); Median (Q1, Q3)\u003c/p\u003e \u003cp\u003eAbbreviation: ANT\u0026thinsp;=\u0026thinsp;Anterior Nucleus of the Thalamus, BNST-AC\u0026thinsp;=\u0026thinsp;Bed Nucleus of the Stria Terminalis Anterior Commissure, CM-Spv-Voi\u0026thinsp;=\u0026thinsp;Centromedian Nucleus-Substantia Periventricularis-Nucleus Ventro-oralis Nucleus, GPi\u0026thinsp;=\u0026thinsp;Globus Pallidus Internus, ICH\u0026thinsp;=\u0026thinsp;Intracranial hemorrhage, OCD\u0026thinsp;=\u0026thinsp;Obsessive-Compulsive Disorder, PD\u0026thinsp;=\u0026thinsp;Parkinson\u0026rsquo;s disease, PSA\u0026thinsp;=\u0026thinsp;Posterior Subthalamic Area, SM\u0026thinsp;=\u0026thinsp;Sclerosis Multiplex, STN\u0026thinsp;=\u0026thinsp;Subthalamic Nucleus, Vao-Vop\u0026thinsp;=\u0026thinsp;ventral oral anterior/posterior nucleus of thalamus, VIM\u0026thinsp;=\u0026thinsp;Ventral Intermediate Nucleus of the Thalamus\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eNon-surgical risk factors related to ICH development\u003c/h3\u003e\n\u003cp\u003eAntithrombotic therapy was taken by 69 patients (10%) in the entire cohort. In univariate regression analyses, antithrombotic therapy was the only statistically significant predictor of any ICH (OR\u0026thinsp;=\u0026thinsp;4.14, p\u0026thinsp;=\u0026thinsp;0.002). Also in multivariable model, antithrombotic therapy remained a statistically significant predictor of any ICH (OR\u0026thinsp;=\u0026thinsp;3.75, p\u0026thinsp;=\u0026thinsp;0.006). Other non-surgical predictors like age at surgery, sex, diagnosis, symptom duration in univariate and also in multivariate analyses were not associated with increased risk of any ICH. Compared to patients without ICH, those with ICH were more often male (71% vs. 62%), whereas age at surgery and symptom duration were similar between groups.\u003c/p\u003e \u003cp\u003eSymptomatic ICH was significantly associated with antithrombotic therapy (OR\u0026thinsp;=\u0026thinsp;4.00, p\u0026thinsp;=\u0026thinsp;0.010). Also in the multivariate model, only antithrombotic therapy remained a significant predictor (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e4\u003c/span\u003e). In symptomatic ICH, sex, diagnosis and duration of symptoms were associated with increased risk of symptomatic ICH but the correlations in univariate and multivariate models were not significant.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRare events logistic regression for symptomatic ICH\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eOutcome: symptomatic intracerebral hemorrhage\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eCharacteristic\u003c/b\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003eUnivariate models\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003e\u003cb\u003eMultivariable model\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eOdds Ratio\u003c/b\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e95% CI\u003c/b\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003ep-value\u003c/b\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eOdds Ratio\u003c/b\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e95% CI\u003c/b\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003ep-value\u003c/b\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.98, 1.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.460\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.98, 1.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.562\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale sex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.73, 4.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.222\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.68, 3.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.369\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntithrombotic therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.44, 9.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.62, 9.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.33, 1.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.715\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.30, 1.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.312\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMER\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.06, 7.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.037\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.94, 4.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.072\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eAbbreviation: CI\u0026thinsp;=\u0026thinsp;Confidence Interval, MER\u0026thinsp;=\u0026thinsp;Microelectrode Recording\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u0026nbsp;All models adjusted for number of DBS implanted.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eSurgical risk factors related to ICH development\u003c/h2\u003e \u003cp\u003eIn univariate regression analyses, MER, and the number of brain penetrations performed by microelectrodes were associated with increased ICH risk but did not reach statistical significance (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Symptomatic ICH was significantly associated with MER (OR\u0026thinsp;=\u0026thinsp;2.64, p\u0026thinsp;=\u0026thinsp;0.037), and number of brain penetrations (OR\u0026thinsp;=\u0026thinsp;1.27, p\u0026thinsp;=\u0026thinsp;0.0019). However, in the multivariate model, there were no surgical predictors for development of symptomatic ICH (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRare events logistic regression for any ICH\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eOutcome: any intracerebral hemorrhage\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eCharacteristic\u003c/b\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003eUnivariate models\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003e\u003cb\u003eMultivariable model\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eOdds Ratio\u003c/b\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e95% CI\u003c/b\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003ep-value\u003c/b\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eOdds Ratio\u003c/b\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e95% CI\u003c/b\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003ep-value\u003c/b\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.99, 1.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.474\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.98, 1.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.562\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale sex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.73, 3.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.272\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.68, 3.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.369\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntithrombotic therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.77, 9.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.62, 9.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.43, 1.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.799\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.30, 1.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.312\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMER\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.90, 4.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.092\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.94, 4.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.072\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eAbbreviation: CI\u0026thinsp;=\u0026thinsp;Confidence Interval, MER\u0026thinsp;=\u0026thinsp;Microelectrode Recording\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u0026nbsp;All models adjusted for number of DBS implanted.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAmong patients with ICH, 29 underwent simultaneous bilateral implantation (ICH rate per lead: 3,9%) and 4 underwent unilateral implantation (ICH rate per lead: 2,7%). There were no instances of ICH among those patients who underwent staged bilateral implantations. Compared to patients who underwent simultaneous bilateral implantations, those who underwent staged procedures were more often male (69% vs. 59%) and older (64 vs. 53 years) and had PD more often (92% vs. 70%). Moreover, in these patients, we used general anesthesia (4,1% vs. 24%) and MER (5,4% vs. 74%) less often; consequently, we performed fewer brain passes per DBS lead implantation (1.07 vs. 2.36).\u003c/p\u003e \u003cp\u003eIn our investigation, a comprehensive analysis revealed a total of 9 distinct stereotactic targets to treat different neurological or neuropsychiatric diseases. These targets included.: subthalamic nucleus (STN, n\u0026thinsp;=\u0026thinsp;885), globus pallidus internus (GPI, n\u0026thinsp;=\u0026thinsp;201), ventral intermediate nucleus (VIM, n\u0026thinsp;=\u0026thinsp;54), the anterior nucleus of thalamus (ANT, n\u0026thinsp;=\u0026thinsp;37), posterior subthalamic area (PSA, n\u0026thinsp;=\u0026thinsp;37), centromedian nucleus substantia periventricularis nucleus ventro-oralis nucleus (CM-Spv-Voi, n\u0026thinsp;=\u0026thinsp;6), and ventral oral anterior/posterior nucleus of thalamus (VOA/VOP, n\u0026thinsp;=\u0026thinsp;2), bed nucleus of the stria terminalis anterior commissure (BNST-AC, n\u0026thinsp;=\u0026thinsp;4), hippocampus (hipp, n\u0026thinsp;=\u0026thinsp;1). Each stereotactic target corresponded to the implantation of a single electrode, facilitating precise localization within the brain. Configurations of stereotactic targets varied among patients based on the primary disease and predominant symptoms with bilateral interventions presenting not infrequently diverse combinations. Majority of interventions were observed in patients with PD, often featuring a combination of bilateral STN targeting.\u003c/p\u003e \u003cp\u003eIn the present study, the vast majority of DBS hardware (1173 electrodes; ~96%) was provided by Medtronic. A significantly smaller number of systems were implanted using electrodes from Abbott (n\u0026thinsp;=\u0026thinsp;30) and Boston Scientific (n\u0026thinsp;=\u0026thinsp;20). Due to the substantial imbalance in the distribution of hardware across manufacturers, formal statistical comparison was not feasible. However, no statistically significant difference was observed in the incidence of ICH between the three manufacturers, suggesting that the choice of DBS system did not influence the risk of this complication.\u003c/p\u003e \u003cp\u003e \u003cb\u003eRisk factor analysis for ICH with transient or permanent neurological deficit.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eFurther, we performed risk factor analysis for ICH with transient and permanent neurological deficit. Due to overall lower rate of permanent neurological deficits found in our patients (6 individuals compromising 0.9% of treated patients) we were unable to find risk factors for ICH producing transient or permanent neurological deficits. We observed that symptomatic ICH with permanent neurological deficits was seen exclusively in PD patients targeting the STN.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eStereotactic functional neurosurgical procedures are relatively safe, with low complication rates of permanent morbidity or mortality. Among these, ICH is among the most severe complications in functional neurosurgery. The incidence of ICH as a complication of DBS lead insertion has been reported to range from 0.5 to 6.9% [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e][\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e][\u003cspan additionalcitationids=\"CR7 CR8\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Despite careful placement of the DBS lead, ICH can occur during or after surgery.\u003c/p\u003e \u003cp\u003eRisk factors for ICH can be categorized as patient-specific or surgery-specific. According to the literature, the most convincing patient-specific factors include presence of hypertension, age, and a history of antithrombotic therapy, while surgery-specific factors include trajectory traversing a sulcus or ventricle, as well as the use of intraoperative MER, particularly the number of brain passes made by microelectrodes [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e][\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e][\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Surgical risks can be reduced with well-planned trajectories using modern neuronavigation. Some of the patient-specific risk factors such as hypertension or antiplatelet therapy may be managed by taking appropriate precautions to lower the incidence of ICH in DBS procedures. Hypertensive patients may benefit from general anesthesia for better blood pressure control. Other patient-specific factors such as age, sex are not modifiable and remain controversial as potential risk factors for ICH. Patient-specific factors have been less extensively studied than surgical ones, and different study groups report contradictory results [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e][\u003cspan additionalcitationids=\"CR11 CR12\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn our study, male sex, when compared to patients without ICH, was more frequently associated with ICH, although the difference did not reach statistical significance. Among the 34 patients with ICH, 24 were men (71%). In our cohort of 683 patients, men constituted 62% (425 patients). Yang et al., in a study of 352 PD patients with 686 implanted DBS leads, reported ICH in 11 patients, 10 of whom were men [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. According to the authors, the incidence of ICH in men was significantly higher than that in women (p\u0026thinsp;=\u0026thinsp;0.026). The female to male in Yang\u0026rsquo;s study (157 women versus 195 men) was similar to as our study cohort [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Santos et al. analyzed risk factors for ICH in 277 patients with a total of 585 implanted DBS leads electrodes [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Besides hypertension, male sex was found to increase the likelihood of hemorrhage (2.2- and 2.7-fold higher risk, respectively), but neither factor reached statistical significance and neither was associated with permanent deficits [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Among the 16 ICH cases, 10 were asymptomatic, and 6 produced transient neurological deficits [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the recently published study by Holewijn et al., based on one of the largest cohort to date of 800 PD patients treated with DBS, the authors found that male sex was a significant risk factor for symptomatic ICH [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The study cohort included 507 (63%) men and 293 women, with 22 patients (2,8%) experiencing symptomatic ICH. Among the 800 patients, 5 (0.6%) suffered permanent neurological deficits. Interestingly, of these 5 patients, 4 were women and one man [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In our cohort, permanent neurological deficits were observed in 6 patients (0.9%), including 2 women and 4 men. Men were more severely affected, with 1 death, 1 case of permanent hemiplegia, and 2 cases of hemiparesis. In contrast, the 2 women experienced relatively mild dysarthria. Helmers et al. identified male sex as a risk factor for ICH in a large cohort of 485 patients with 970 leads electrodes implanted [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In contrast, several authors did not find the male sex or sex in general to be significant risk factor for ICH following DBS procedures [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e][\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e][\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e][\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Some studies have suggested that the combination of male sex and hypertension may constitute an enhanced risk for ICH [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e][\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Among all the patient-related risk factors examined, hypertension appears to shows one the most consistent association with ICH in DBS [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e][\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e][\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Hypertension has also been reported as a risk factor in earlier studies evaluating the cumulative experience not only in DBS procedures, but also in ablative functional procedures [\u003cspan additionalcitationids=\"CR8 CR9 CR10\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Xiaowu et al. examined risk factors in a large cohort of 644 patients who underwent lesioning, DBS or both procedures [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The incidence of ICH was 2.5 times higher in hypertensive patients (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) compared in normotensive patients. Gorgulho et al. and Elias et al. also found that hypertension was a significant risk factor for ICH [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e][\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Several other studies have confirmed that hypertension is an important factor in the development of ICH in functional procedures [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e][\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e][\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e][\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. It should be noted that the definition of hypertension varied across studies. Gorgulho et al. defined hypertension as occurring when intraoperative or postoperative systolic blood pressure (BP) reached 160 mmHg or higher [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Sansur et al. classified patients as hypertensive if the diagnosis was documented in the medical record or if patients had a history of antihypertensive treatment [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In the present study, we defined hypertension as a preexisting diagnosis in patients who were taking antihypertensive medication at the time of admission. Among our cohort of 683 patients, 248 (36%) were diagnosed with hypertension; however, the incidence of ICH was similar between hypertensive and normotensive patients. We paid special attention not merely to history of hypertension per se, but to actual blood pressure values during surgery and in the early postoperative period. During DBS procedures, the anesthesiologist maintained intraoperative BP below 130/80 mmHg, and below 140/90 mmHg in the first 24 hours after surgery. In the study, six procedures were aborted due to uncontrolled high BP. These patients were operated on at a later date, mostly under general anesthesia, without hemorrhagic complications. Intraoperative bleeding caused by elevated systolic BP may lead to neurological deficits with altered consciousness and is readily identified on emergency intraprocedural CT. This type of hemorrhage is usually associated with permanent neurological deficits. Shin et al. identified intraoperative SBP as a risk factor for all cases of ICH which resulted in permanent neurological deficits. In their analysis, systolic BP values were evaluated in detail, and a threshold of 129.4 mmHg was identified as the cut-off for the occurrence of ICH [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Moreover, systolic BP greater than 148.3 mmHg was associated with ICH leading to permanent neurological deficits [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Several large-cohort studies also identified male sex and hypertension as key risk factors [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e][\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e][\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Interestingly, most of these studies associate these two patient-specific risk factors primarily with advanced Parkinson\u0026rsquo;s disease [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. However, some studies have found no significant association between hypertension and ICH [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e][\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBesides sex and hypertension, age is also regarded as a possible risk factor for ICH. In our cohort, we did not identify age as a predisposing factor for ICH. There was no difference in the incidence of ICH between patients aged 65 years or younger and those older than 65. Our results regarding age at the time of surgery as a risk factors have been confirmed by other studies [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e][\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e][\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Holewijn et al. did not mention age at surgery as a risk factor for either symptomatic or asymptomatic ICH in PD patients undergoing DBS [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In contrast, several authors have reported that age at surgery plays an important role in incidence of ICH following DBS. Sansur et al. found that in a group of 259 patients, age was significantly associated with ICH, with the mean age of patients with symptomatic ICH being 65 years compared to 41 years in those without ICH [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Patient age at the time of surgery as a risk factor for ICH was also emphasized by Ben-Haim et al., who reported a mean age of 64.2\u0026thinsp;\u0026plusmn;\u0026thinsp;9.5 years in patients with ICH versus 53.3\u0026thinsp;\u0026plusmn;\u0026thinsp;15.9 years in those without [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Similarly, Martin et al. found that older age was a statistically significant risk factor, with the average age of patients with ICH being 64.8 years compared to 57.9 years in the overall cohort (p\u0026thinsp;=\u0026thinsp;0.0125) [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn our study, antithrombotic therapy was used by 69 patients (10%) and was the only statistically significant predictor of ICH in both univariable and multivariable models. In all cases, antithrombotic agents were discontinued at least 10 days prior to the planned DBS procedure. In contrast, Shin et al. also discontinued antithrombotic therapy 10 days before DBS but did not observe an increased risk of ICH [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Similarly, Sansur et al. reported no increased hemorrhagic risk among 23 of 143 patients (16%) with prior antithrombotic use [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Besides the patient-specific risk factors for ICH discussed above, the underlying diagnosis and the anatomical target chosen for DBS may also represent potential risk factors. For statistical purposes, our patient cohort was divided into two groups based on diagnosis: patients with Parkinson\u0026rsquo;s disease (PD group) and patients with other indications (non-PD group), due to diagnostic heterogeneity and the small sample sizes of other disorders. We were unable to identify a higher incidence of ICH between these two groups. Some authors have reported that the diagnosis of PD is associated with a higher risk of ICH compared to patients with dystonia or essential tremor [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e][\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Sansur et al. found that a diagnosis of PD was associated with an increased risk of ICH [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Elias et al. also reported a threefold higher ICH rate in PD vs. dystonia or ET (8% vs. 2.5%), though not statistically significant [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Age differences between diagnostic groups may partly explain this variability. Other authors have likewise concluded that the underlying neurological diagnosis does not influence the risk of ICH in patients undergoing DBS [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e][\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Based on our experience, we did not find a significant association between diagnosis and overall ICH incidence.\u003c/p\u003e \u003cp\u003eDifferent diagnoses are treated using different anatomical targets for DBS. Patients with PD are typically treated by implanting DBS electrodes into the STN, depending on clinical symptoms, or less frequently into the GPi. In tremor-dominant PD, the PSA may also be used. In patients with dystonia, the targets include the GPi or, less commonly, the STN. Essential tremor is usually treated with DBS targeting the Vim or the PSA. To determine whether a particular anatomical target carries a higher risk of ICH, such a study would need to be conducted in a homogeneous group of patients with the same diagnosis. In our cohort, we were unable to correlate any specific anatomical target with an increased risk of overall ICH. However, as mentioned earlier, symptomatic ICH with permanent neurological deficits occurred exclusively in PD patients. Other studies have also failed to find significant differences in ICH risk based on anatomical target [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e][\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Binder et al. reported that the GPi target may be more vulnerable to ICH due to the presence of lenticulostriate vessels in the target area, compared with the STN [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Another potential source of bleeding during GPi targeting is injury to vessels in the cisternal space around the optic tract, caused by microelectrodes or macroelectrodes [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. The burr holes used for GPi targeting are generally placed more posteriorly. Bridging veins may be injured during burr hole drilling or dural opening, potentially leading to delayed venous infarction. Such complications have been described in the literature [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Despite the above-mentioned risks, some authors consider GPi targeting to be safer than STN [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The trajectory to the GPi is shorter than that to the STN, as the STN lies deeper within the brain. A shorter intracerebral path may reduce the risk of bleeding. ICH occurring during GPi targeting typically affects the basal ganglia, whereas STN targeting may lead to hemorrhage in the thalamus or mesencephalon. STN-related ICH is more often associated with permanent neurological deficits and can be fatal [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. In our series, all cases of permanent neurological deficits due to ICH occurred in PD patients who were targeted at the STN, including one death. Our findings may suggest that STN targeting is associated with a higher risk of ICH resulting in permanent neurological deficits compared to GPi (although this could not be confirmed statistically). Other authors have reported that while the overall incidence of ICH between STN and GPi targets is similar, permanent neurological deficits are more frequently observed with STN targeting in PD patients [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Sorer et al. did not find any patient-specific risk factors, including sex, age, diagnosis, anatomical target, or device manufacturer, to be associated with an increased incidence of complications, including ICH [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. In contrast, surgical experience was found to be significantly associated with complication rates (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Other studies have also concluded that the experience of the surgical team plays a crucial role in reducing the overall rate of DBS-related complications, including ICH [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. We support this conclusion, as we observed no permanent neurological deficits due to ICH in our last 350 patients.\u003c/p\u003e \u003cp\u003eThere are some limitations in our study. Our 17-year retrospective period encompassed some changes in surgical technique and imaging protocols. The strict scheduled intraprocedural stereotactic CT was introduced from January 2018 and before this period postoperative CT was done at various time intervals after DBS. Consequently, some silent hemorrhages may have gone undetected in our earlier years spanning period from 2008 to 2017. Due to the relatively small number of hemorrhagic events in our cohort, particularly those resulting in permanent neurological deficits (6 patients out of 683), we were unable to perform certain statistical analyses that could be generalized to the broader population. This limitation is common among studies investigating rare adverse events. To increase statistical robustness for selected features, we grouped relevant variables where appropriate, such as combining diagnoses into PD and non-PD categories. In cases where statistical analysis was not feasible, descriptive reporting was used. As a result, some of the associations observed in this study should be interpreted with caution.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eDBS procedures demonstrate an overall favorable safety profile, with an ICH prevalence of approximately 4.98% and a low incidence of permanent neurological deficits, affecting only 0.9% of treated patients. Our analysis revealed a statistically significant association between certain patient-specific risk factors and ICH, indicating that preoperative antithrombotic therapy remained a significant predictor of hemorrhagic complications. Other non-surgical and surgical risk factors analyzed including sex, age at surgery, diagnosis, symptom duration, presence of hypertension, use of MER, number of guiding microelectrodes utilized, and type of anesthesia, were not identified as predictors of overall ICH. Although the diagnosis of PD and targeting of the STN were observed exclusively in patients who developed permanent neurological deficits, these factors were not statistically significant in relation to the overall ICH rate in the present analysis. Strict intraprocedural and scheduled postoperative CT or MRI may help detect a greater number of asymptomatic ICH cases. The risk of ICH appears to be influenced by a combination of factors, which can be grouped into three categories: patient-specific factors, surgery-specific factors, and the experience of the surgical team. Further studies are needed to better determine the true incidence of ICH, with particular emphasis on reducing events that result in permanent neurological deficits.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKarol Karamon: Conceptualization, Methodology, Formal analysis, Investigation, Data curation, Writing - Original Draft, Visualization\u003c/p\u003e\n\u003cp\u003eMichał Sobstyl: Methodology, Validation, Investigation, Resources, Writing - Review \u0026amp; Editing, Supervision, Project administration\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eŁukasz Smoliński: Methodology, Formal analysis, Writing - Review \u0026amp; Editing, Visualization\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo financial support was received for the conduct of this research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data relevant to this study are included in the manuscript, including summarized results presented in tables. Due to institutional and ethical restrictions related to patient confidentiality, the raw datasets are not publicly available. Additional information may be obtained from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective study involved analysis of anonymized clinical data collected as part of routine care. According to institutional and national regulations, ethical committee approval and informed consent were not required.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClinical trial number: not applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHariz M, Blomstedt P (2022) Deep brain stimulation for Parkinson's disease. 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Arch Gen Psychiatry 64(2):170\u0026ndash;176. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/archpsyc.64.2.170\u003c/span\u003e\u003cspan address=\"10.1001/archpsyc.64.2.170\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSobstyl M, Brzuszkiewicz-Kuźmicka G, Aleksandrowicz M, Pasterski T (2019) Large Hemorrhagic Cerebral Venous Infarction due to Deep Brain Stimulation Leads Placement. Report of 2 Cases. Turk Neurosurg 29(4):611\u0026ndash;614. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.5137/1019-5149.JTN.22281-17.3\u003c/span\u003e\u003cspan address=\"10.5137/1019-5149.JTN.22281-17.3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSorar M, Hanalioglu S, Kocer B, Eser MT, Comoglu SS, Kertmen H (2018) Experience Reduces Surgical and Hardware-Related Complications of Deep Brain Stimulation Surgery: A Single-Center Study of 181 Patients Operated in Six Years. \u003cem\u003eParkinsons Dis\u003c/em\u003e. ;2018:3056018. Published 2018 Jul 22. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1155/2018/3056018\u003c/span\u003e\u003cspan address=\"10.1155/2018/3056018\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"neurosurgical-review","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nrev","sideBox":"Learn more about [Neurosurgical Review](https://www.springer.com/journal/10143)","snPcode":"10143","submissionUrl":"https://submission.nature.com/new-submission/10143/3","title":"Neurosurgical Review","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Deep Brain Stimulation, Intracranial Hemorrhage, Antithrombotic Therapy, Functional Neurosurgery","lastPublishedDoi":"10.21203/rs.3.rs-8575448/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8575448/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction\u003c/h2\u003e \u003cp\u003eDeep brain stimulation (DBS) is an established neurosurgical therapy for movement disorders, neuropsychiatric conditions, and drug-resistant epilepsy. Intracranial hemorrhage (ICH) remains among the most severe complications of DBS, with limited data on its risk factors. This study aims to assess the incidence of ICH and evaluate associated non-surgical and selected surgical risk factors in a large, single-center cohort.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe retrospectively analyzed 683 patients (1227 DBS electrodes implanted) treated at a single medical center between November 2008 and April 2025. Data on demographics, diagnoses, comorbidities, and surgical techniques were collected and analyzed using both statistical and descriptive methods to identify predictors of ICH. Hemorrhages were classified as symptomatic (transient or permanent) or asymptomatic based on clinical outcome.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eICH occurred in 34 patients (4.98%), with 40 hemorrhagic events in total (3.26% per lead). Permanent neurological deficits occurred in 6 patients (0.9%). Antithrombotic therapy was the only statistically significant predictor of ICH in both univariate and multivariate models (OR\u0026thinsp;=\u0026thinsp;4.14, p\u0026thinsp;=\u0026thinsp;0.002; OR\u0026thinsp;=\u0026thinsp;3.75, p\u0026thinsp;=\u0026thinsp;0.006). Microelectrode recording (MER) and number of brain penetrations were associated with symptomatic ICH in univariate analysis but lost significance in multivariate models. No associations were found for sex, age, hypertension, diagnosis, or stereotactic target. Subthalamic nucleus targeting was observed exclusively in patients with permanent deficits.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eDBS remains a safe procedure with low risk of permanent ICH-related morbidity. Antithrombotic therapy is a modifiable risk factor. Continued refinement in perioperative planning and surgical technique is essential to further minimize hemorrhagic risk.\u003c/p\u003e","manuscriptTitle":"Hemorrhagic complications in deep brain stimulation: analysis of non-surgical risk factors in a cohort of 683 patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-02 07:55:03","doi":"10.21203/rs.3.rs-8575448/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-10T17:49:24+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-09T05:43:21+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-06T14:31:44+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-05T19:19:00+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-04T07:44:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"246567047282874798413838302124582996841","date":"2026-02-03T14:37:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"96386830588932652504423528590810176749","date":"2026-02-03T10:14:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"36857765372825012016421504488892762268","date":"2026-02-01T22:42:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"197443497206924905486485319965361228682","date":"2026-02-01T03:22:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"156012569384789841776910965553461462602","date":"2026-01-31T13:13:01+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-31T00:24:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"249047011460156548738240704938437864163","date":"2026-01-31T00:12:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"36511177188151568740118028508312956506","date":"2026-01-30T15:49:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"183315024187210252887847440846689492110","date":"2026-01-30T11:44:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"318647581797518927274701401195299754486","date":"2026-01-29T17:22:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"65328097943524316894512289797884434438","date":"2026-01-29T17:08:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"150384369882645094961152482818084125767","date":"2026-01-29T15:47:51+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-29T13:51:52+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-27T22:32:46+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-13T09:23:19+00:00","index":"","fulltext":""},{"type":"submitted","content":"Neurosurgical Review","date":"2026-01-11T19:14:34+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"neurosurgical-review","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nrev","sideBox":"Learn more about [Neurosurgical Review](https://www.springer.com/journal/10143)","snPcode":"10143","submissionUrl":"https://submission.nature.com/new-submission/10143/3","title":"Neurosurgical Review","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"8ff3f889-1c88-4331-825f-b9e132c9f28f","owner":[],"postedDate":"February 2nd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-04-20T16:01:50+00:00","versionOfRecord":{"articleIdentity":"rs-8575448","link":"https://doi.org/10.1007/s10143-026-04226-9","journal":{"identity":"neurosurgical-review","isVorOnly":false,"title":"Neurosurgical Review"},"publishedOn":"2026-04-15 15:58:09","publishedOnDateReadable":"April 15th, 2026"},"versionCreatedAt":"2026-02-02 07:55:03","video":"","vorDoi":"10.1007/s10143-026-04226-9","vorDoiUrl":"https://doi.org/10.1007/s10143-026-04226-9","workflowStages":[]},"version":"v1","identity":"rs-8575448","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8575448","identity":"rs-8575448","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}