DOI: https://doi.org/https://doi.org/10.57187/s.3855
Accuracy is key. This statement obviously applies to neurosurgery in general, but probably even more so for deep brain stimulation (DBS) surgery in particular. The goal is to modulate the function of a very specific pre-defined group of dysfunctional brain cells – in an area which is typically very small and deeply located – to provide clinical benefit. The more dysfunctional cells are modulated, the greater the benefit. On the other hand, normally functioning neighbouring cells should be spared to avoid side-effects. Here, the smaller the target and the closer the surrounding healthy structures, the thinner the line between optimal and non-optimal results – and the more important the role of maximal accuracy.
DBS in the subthalamic nucleus (STN) for the treatment of Parkinson’s disease is a paramount example of the importance of accuracy. While the subthalamic nucleus has many advantages over alternative nuclei with regard to efficacy [1], it is also a particularly delicate target with regard to side-effects, given its small size and close proximity to critical structures such as the corticospinal tract [2]. In addition, the subthalamic nucleus is not homogeneous but consists of functionally distinct subdivisions that cannot be visualised by MRI. Here, the precise stimulation spot within the dorsal motor subthalamic nucleus is considered the single most important predictor of treatment success, even more important than levodopa response or disease duration [3].
To maximise accuracy and optimise clinical outcome, STN-DBS lead implantation has traditionally been performed in the awake patient under local anaesthesia [4–6]. Here, wakefulness has been considered critical for high-quality microelectrode recording to electrophysiologically map the subthalamic nucleus and for test stimulation to assess efficacy and side-effects [4, 6]. In case of suboptimal test results, the lead can be relocated intraoperatively.
Today, more and more DBS centres are dispensing with wakefulness and perform asleep implantations under general anaesthesia instead [7]. This development is remarkable because it contrasts with the growing understanding of the paramount value of lead localisation in STN-DBS surgery. Also, it is not without a certain irony that the exact opposite trend can be observed in other neurosurgical subspecialties, e.g. neuro-oncology, where the use of awake surgery is steadily expanding [8].
The supporters of asleep DBS claim that it is equally effective yet less troublesome as compared to the awake approach. We disagree with this statement and want to present our arguments that awake interventions (1) offer an important extra benefit in providing maximal efficacy with minimal side effects, defining a more favorable therapeutic window, (2) are less burdensome than many assume, provided support is optimal, and (3) therefore offer a superior benefit-cost ratio for many patients.
As a first step, we must acknowledge that the scientific literature on awake versus asleep STN-DBS surgeries is currently inconclusive. While some studies report no significant differences in efficacy and safety outcomes [9–14], others demonstrate a lower rate of side-effects following awake intervention [7]. Also, the largest prospective randomised trial to date, the GALAXY trial, was not designed and powered to solve this issue but primarily tested the hypothesis that awake interventions increase the risk for neuropsychiatric adverse effects – which, however, had to be rejected [13]. Moreover, the unexpected finding of an increased rate of brain haemorrhages in the asleep group raises questions regarding the study’s validity [13]. Thus, the controversy is not (yet) settled, as the supporters of the asleep approach claim, but remains a matter of debate. So, what arguments are there to support awake STN-DBS implantations?
First, operating on fully awake patients reduces the risk of lead misplacement, in a strict sense, outside the subthalamic nucleus, e.g. due to intraoperative brain shift [15], MRI-CT fusion errors [16] or other technical problems. Given that it is the last of many steps before final implantation, intraoperative test stimulation is the ultimate safety measure to confirm correct lead positioning.
Second, wakefulness also increases the chance for maximal benefit through optimal lead placement at the best possible spot within the subthalamic nucleus. Most importantly, it allows assessment of both efficacy and side-effect thresholds (including subtle ones [2]) and, thus, identification of the full therapeutic window of a given stimulation site. If the efficacy or side-effect profile is not optimal, other sites can be tested. This is particularly helpful when two microelectrode recording trajectories show good subthalamic nucleus signals, as therapeutic windows of different stimulation sites can be directly compared (see video). We systematically examined the Zurich outcomes and found that at least one of nine patients benefits from this approach by receiving a corrected and optimised final lead placement [17].
Moreover, wakefulness provides higher-quality microelectrode recordings to sharply delineate the borders of the subthalamic nucleus [18]. This facilitates targeting of the neighbouring zona incerta and substantia nigra to treat dyskinesia [19, 20] or gait freezing [18] through interleaved co-stimulation. Importantly, as the disease progresses over time, therapy demands change. Thus, a given lead localisation may be satisfactory at the beginning but unsatisfactory at a later disease stage when a certain clinical demand is impossible to meet.
Supporters of asleep STN-DBS implantations claim that recent advances in stimulation technologies compensate for imperfect lead localisation. However, neither directional stimulation [21] nor brain sensing seem to significantly enlarge a given therapeutic window – and both tools are, for sure, no adequate substitute for a significantly misplaced lead [8]. Moreover, while probably every tool, including these new ones, adds a certain degree of benefit, it is the sum that is decisive – and why should we deliberately waive arguably the most powerful tool?
While we must admit that awake STN-DBS implantations are possibly more burdensome for most patients and slightly more expensive than asleep interventions, the question is whether this outweighs the benefits.
First, the psychological load of an awake operation is probably not as heavy as many assume. When patients were questioned after surgery, overall satisfaction did not significantly differ between awake and asleep groups despite higher rates of discomfort and anxiety in the awake group [22]. Of note, only 28% of awake patients would have preferred to be operated upon under general anaesthesia, indicating that 72% were positive about awake surgery. On the other hand, at least 12% in the asleep group would have favoured an awake approach [22]. This demonstrates that patient preferences are heterogeneous and underlines the importance of good education, preparation and psychological support [23]. Here, the role of a trustful relationship between patients and their medical team cannot be overestimated. Indeed, the challenge of an awake operation may also be a chance to grow together as a team including patients, caregivers, nurses, neurologists and neurosurgeons. Additionally, other measures can be applied to improve patient comfort, including short-acting sedatives such as remifentanil [13, 24] to bypass parts of the operation where wakefulness is dispensable and to reduce the duration of full wakefulness to a minimum if this is necessary. Accordingly, in >500 patients operated under local anaesthesia in Zurich – often with significant disease burden and advanced age – we only once had a panic reaction, obliging us to “change gear” and administer general anaesthesia.
Second, the risk of surgical complications such as intracranial haemorrhage is not increased by remaining awake. A positive correlation was found between bleeding risk and the number of microelectrode recording trajectories [25]. However, microelectrode recording was applied in roughly every second trial on asleep DBS [7] and is, thus, used independently of the anaesthesia method. One could even argue that waiving test stimulation increases the need for multiple microelectrode recording trajectories, which further fuels the bleeding risk. Moreover, the GALAXY trial has shown that awake operations do not carry a higher risk of postoperative confusion and subsequent neuropsychiatric sequelae [13], possibly because the burden of wakefulness is compensated by the burden of longer-lasting general anaesthesia in the asleep group [26].
Third, while microelectrode recording (independently of the anaesthesia method) and test stimulation increase operation time [13] – albeit by not more than 26 minutes (!) on average [13] – other tools such as surgical robots [27] or intraoperative imaging can be applied to shorten it again [27] and reduce costs.
Based on these arguments, we are convinced that the benefits of awake surgery clearly outweigh the costs that are on average lower than many assume. This positive benefit-cost calculation particularly holds true in the long run. To put it another way, the few, possibly burdensome, extra hours of staying awake pale into insignificance when compared to the days, weeks, months and years of suffering due to insufficient therapy or the burden of searching for the right stimulation settings given a suboptimal lead position.
Nevertheless, we must admit that awake STN-DBS is not suitable for everyone. Hence, we should beware of being dogmatic and solely sticking to one method – instead we should practice personalised medicine. The question is: What is your primary choice and how do you communicate with patients? In this context, we warn against oversimplified advertisements praising the comfort of asleep interventions while claiming that there is no “proven” extra benefit of staying awake. Clearly, it is much more time-consuming and cumbersome to rationally inform a patient about this complex matter. However, in the interests of our patients, we are convinced that it is worth it!
The patient shown in the video provided her informed consent for this video to be publishedto be published to accompany this article.
All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflict of interest related to the content of this manuscript was disclosed.
1.Hariz M, Blomstedt P. Deep brain stimulation for Parkinson’s disease. J Intern Med. 2022 Nov;292(5):764–78.
2. Koeglsperger T, Palleis C, Hell F, Mehrkens JH, Bötzel K. Deep Brain Stimulation Programming for Movement Disorders: Current Concepts and Evidence-Based Strategies. Front Neurol. 2019 May;10:410.
3. Horn A, Reich M, Vorwerk J, Li N, Wenzel G, Fang Q, et al. Connectivity Predicts deep brain stimulation outcome in Parkinson disease. Ann Neurol. 2017 Jul;82(1):67–78.
4. Pollak P, Krack P, Fraix V, Mendes A, Moro E, Chabardes S, et al. Intraoperative micro- and macrostimulation of the subthalamic nucleus in Parkinson’s disease. Mov Disord. 2002;17(S3 Suppl 3):S155–61.
5. Deuschl G, Schade-Brittinger C, Krack P, Volkmann J, Schäfer H, Bötzel K, et al.; German Parkinson Study Group, Neurostimulation Section. A randomized trial of deep-brain stimulation for Parkinson’s disease. N Engl J Med. 2006 Aug;355(9):896–908.
6. Gross RE, Krack P, Rodriguez-Oroz MC, Rezai AR, Benabid AL. Electrophysiological mapping for the implantation of deep brain stimulators for Parkinson’s disease and tremor. Mov Disord. 2006 Jun;21(S14 Suppl 14):S259–83.
7. Ho AL, Ali R, Connolly ID, Henderson JM, Dhall R, Stein SC, et al. Awake versus asleep deep brain stimulation for Parkinson’s disease: a critical comparison and meta-analysis. J Neurol Neurosurg Psychiatry. 2018 Jul;89(7):687–91.
8. Wang D, Ashkan K. “Grass Is Always Greener on the Other Side” or Is It?! Comparison of Trend of Awake Craniotomy in Neuro-Oncology and Asleep Deep Brain Stimulation. Stereotact Funct Neurosurg. 2023;101(3):217–20.
9. Jin H, Gong S, Tao Y, Huo H, Sun X, Song D, et al. A comparative study of asleep and awake deep brain stimulation robot-assisted surgery for Parkinson’s disease. NPJ Parkinsons Dis. 2020 Oct;6(1):27.
10. Chen T, Mirzadeh Z, Chapple KM, Lambert M, Shill HA, Moguel-Cobos G, et al. Clinical outcomes following awake and asleep deep brain stimulation for Parkinson disease. J Neurosurg. 2018 Mar;130(1):109–20.
11. Chen T, Mirzadeh Z, Chapple K, Lambert M, Ponce FA. Complication rates, lengths of stay, and readmission rates in “awake” and “asleep” deep brain simulation. J Neurosurg. 2017 Aug;127(2):360–9.
12. Brodsky MA, Anderson S, Murchison C, Seier M, Wilhelm J, Vederman A, et al. Clinical outcomes of asleep vs awake deep brain stimulation for Parkinson disease. Neurology. 2017 Nov;89(19):1944–50.
13. Holewijn RA, Verbaan D, van den Munckhof PM, Bot M, Geurtsen GJ, Dijk JM, et al. General Anesthesia vs Local Anesthesia in Microelectrode Recording-Guided Deep-Brain Stimulation for Parkinson Disease: The GALAXY Randomized Clinical Trial. JAMA Neurol. 2021 Oct;78(10):1212–9.
14. Engelhardt J, Caire F, Damon-Perrière N, Guehl D, Branchard O, Auzou N, et al. A Phase 2 Randomized Trial of Asleep versus Awake Subthalamic Nucleus Deep Brain Stimulation for Parkinson’s Disease. Stereotact Funct Neurosurg. 2021;99(3):230–40.
15. Ivan ME, Yarlagadda J, Saxena AP, Martin AJ, Starr PA, Sootsman WK, et al. Brain shift during bur hole-based procedures using interventional MRI. J Neurosurg. 2014 Jul;121(1):149–60.
16. Burke JF, Tanzillo D, Starr PA, Lim DA, Larson PS, Image Fusion Error MR. CT and MRI Image Fusion Error: An Analysis of Co-Registration Error Using Commercially Available Deep Brain Stimulation Surgical Planning Software. Stereotact Funct Neurosurg. 2021;99(3):196–202.
17. Krauss P, Oertel MF, Baumann-Vogel H, et al. Intraoperative Neurophysiologic Assessment in Deep Brain Stimulation Surgery and its Impact on Lead Placement. J Neurol Surg A Cent Eur Neurosurg. 2021;82(01):018-026. doi:
18. Zhao GR, Cheng YF, Feng KK, Wang M, Wang YG, Wu YZ, et al. Clinical Study of Intraoperative Microelectrode Recordings during Awake and Asleep Subthalamic Nucleus Deep Brain Stimulation for Parkinson’s Disease: A Retrospective Cohort Study. Brain Sci. 2022 Oct;12(11):1469.
19. Bouthour W, Béreau M, Kibleur A, Zacharia A, Tomkova Chaoui E, Fleury V, et al. Dyskinesia-inducing lead contacts optimize outcome of subthalamic stimulation in Parkinson’s disease. Mov Disord. 2019 Nov;34(11):1728–34.
20. Aquino CC, Duffley G, Hedges DM, Vorwerk J, House PA, Ferraz HB, et al. Interleaved deep brain stimulation for dyskinesia management in Parkinson’s disease. Mov Disord. 2019 Nov;34(11):1722–7.
21. Debove I, Petermann K, Nowacki A, Nguyen TK, Tinkhauser G, Michelis JP, et al. Deep Brain Stimulation: When to Test Directional? Mov Disord Clin Pract. 2023 Feb;10(3):434–9.
22. LaHue SC, Ostrem JL, Galifianakis NB, San Luciano M, Ziman N, Wang S, et al. Parkinson’s disease patient preference and experience with various methods of DBS lead placement. Parkinsonism Relat Disord. 2017 Aug;41:25–30.
23. Falconer RA, Rogers SL, Brewer CM, Piscitani F, Shenai MB. Presurgical Rehearsals for Patients Considering “Awake” Deep Brain Stimulation. Front Surg. 2016 Aug;3:44. [cited 2023 Nov 4] Available from: https://www.frontiersin.org/articles/10.3389/fsurg.2016.00044
24. Bos MJ, de Korte-de Boer D, Alzate Sanchez AM, Duits A, Ackermans L, Temel Y, et al. Impact of Procedural Sedation on the Clinical Outcome of Microelectrode Recording Guided Deep Brain Stimulation in Patients with Parkinson’s Disease. J Clin Med. 2021 Apr;10(8):1557.
25. Rasiah NP, Maheshwary R, Kwon CS, Bloomstein JD, Girgis F. Complications of Deep Brain Stimulation for Parkinson Disease and Relationship between Micro-electrode tracks and hemorrhage: Systematic Review and Meta-Analysis. World Neurosurg. 2023 Mar;171:e8–23.
26. Huang HW, Zhang GB, Li HY, Wang CM, Wang YM, Sun XM, et al. Development of an early prediction model for postoperative delirium in neurosurgical patients admitted to the ICU after elective craniotomy (E-PREPOD-NS): A secondary analysis of a prospective cohort study. J Clin Neurosci. 2021 Aug;90:217–24.
27. Giridharan N, Katlowitz KA, Anand A, Gadot R, Najera RA, Shofty B, et al. Robot-Assisted Deep Brain Stimulation: High Accuracy and Streamlined Workflow. Oper Neurosurg (Hagerstown). 2022 Sep;23(3):254–60.