Introduction: Deep brain stimulation (DBS) is a well-established surgical therapy for patients with Parkinsons’ Disease (PD). Traditionally, DBS surgery for PD is performed under local anesthesia, whereby the patient is awake to facilitate intraoperative neurophysiological confirmation of the intended target using microelectrode recordings. General anesthesia allows for improved patient comfort without sacrificing anatomic precision and clinical outcomes. Methods: We performed a systemic review and meta-analysis on patients undergoing DBS for PD. Published randomized controlled trials, prospective and retrospective studies, and case series which compared asleep and awake techniques for patients undergoing DBS for PD were included. A total of 19 studies and 1,900 patients were included in the analysis. Results: We analyzed the (i) clinical effectiveness – postoperative UPDRS III score, levodopa equivalent daily doses and DBS stimulation requirements. (ii) Surgical and anesthesia related complications, number of lead insertions and operative time (iii) patient’s quality of life, mood and cognitive measures using PDQ-39, MDRS, and MMSE scores. There was no significant difference in results between the awake and asleep groups, other than for operative time, for which there was significant heterogeneity. Conclusion: With the advent of newer technology, there is likely to have narrowing differences in outcomes between awake or asleep DBS. What would therefore be more important would be to consider the patient’s comfort and clinical status as well as the operative team’s familiarity with the procedure to ensure seamless transition and care.

Deep brain stimulation (DBS) is a well-established surgical therapy for patients with advanced levodopa (l-dopa)-responsive forms of Parkinson’s [1] disease (PD), allowing for dramatic reductions in both motor fluctuations and dyskinesia [1‒5]. The success of postoperative clinical outcome depends on appropriate patient selection, optimal targeting of the intended nuclei [1, 2], and long-term optimization of stimulation variables [3, 5, 6].

Traditionally, DBS surgery for PD is performed under local anesthesia, whereby the patient is awake to facilitate intraoperative neurophysiological confirmation of the intended target using microelectrode recording (MER) [2, 3, 7] as well as clinical evaluation of induced improvement of parkinsonian signs with test stimulation [8, 9]. In this article, this method will henceforth be termed as “awake.” Proponents of this awake technique argue that functional accuracy as determined by intraoperative electrophysiological and clinical test stimulation to assess for benefit and adverse effects are critical for optimizing DBS outcomes and minimizing treatment-related side effects [7, 10].

Conversely, many studies have since reported successful clinical outcomes with DBS insertion under general anesthesia (GA) [10]. Typically, intraoperative imaging is co-registered with a preoperative brain magnetic resonance imaging plan to visualize the intended target, plan the appropriate trajectory and confirm lead placement. Intraoperative neurophysiological recording with MER may or may not be used, according to the surgeon or institution’s preference. This method is termed “asleep” in this paper. Although there are concerns that GA may affect MER recordings, advocates for asleep DBS techniques maintain that GA allows for improved patient comfort [3], decreased complication rates, operative times and costs without sacrificing anatomic precision and clinical outcomes [1, 3], with potential improvement especially in regard to speech fluency and quality of life [11].

We have thus performed a systematic review and meta-analysis to assess the current evidence including all cohort studies to compare the clinical, surgical, and quality of life outcomes for patients undergoing DBS for idiopathic PD under asleep and awake techniques. Prior to our study, there has been three meta-analysis comparing awake and asleep DBS surgery. Table 1 is a summary of the previous meta-analysis and their findings. The prior meta-analysis included mostly small retrospective studies with no control groups. Since the latest meta-analysis by Liu et al. in 2019 [10], there have been two large landmark randomized controlled trials conducted on a total of 140 patients [13, 14]. The newer studies also included quality of life indices [13‒15] such as the Mattis Dementia Rating Scale (MDRS), Parkinsons’ Disease Questionnaire-39 (PDQ-39), and Mini-Mental State Examination (MMSE), which were not analyzed in the older meta-analyses.

Table 1.

A summary of prior systematic review and meta-analysis comparing asleep versus awake DBS surgery for PD

AuthorHo et al. [7]Sheshadri et al. [12]Liu et al. [10]
Year published 2018 2017 2020 
Journal Journal of Neurology, Neurosurgery and Psychiatry The Canadian Journal of Neurological Sciences Stereotactic and Functional Neurosurgery 
Systematic review and meta-analysis Systematic review and meta-analysis Systematic review and meta-analysis 
Date of inclusion 2004–2015 2007–2015 2004–2019 
No. of studies 145 14 
Retrospective cohort studies 70 14 
Case series, cohort studies 79 
Randomized controlled trial 
Patients, n 8,382 455 1,523 
Asleep 7,771 194 967 
Awake 671 261 556 
AuthorHo et al. [7]Sheshadri et al. [12]Liu et al. [10]
Year published 2018 2017 2020 
Journal Journal of Neurology, Neurosurgery and Psychiatry The Canadian Journal of Neurological Sciences Stereotactic and Functional Neurosurgery 
Systematic review and meta-analysis Systematic review and meta-analysis Systematic review and meta-analysis 
Date of inclusion 2004–2015 2007–2015 2004–2019 
No. of studies 145 14 
Retrospective cohort studies 70 14 
Case series, cohort studies 79 
Randomized controlled trial 
Patients, n 8,382 455 1,523 
Asleep 7,771 194 967 
Awake 671 261 556 
Results
UPDRS III improvement No difference Data suggest a trend toward improved UPDRS III score under awake technique, though statistically insignificant No difference 
Postoperative LEDD No difference No difference No difference 
Adverse events Not reported No difference No difference 
Adverse effects – related to stimulation Stimulation-related effects less in awake versus asleep No difference No difference 
Adverse effects – intracranial hemorrhage Rate of intracranial hemorrhage was lower in asleep group Not reported No difference 
Adverse effects – speech disturbances Not reported Not reported No difference 
Operating time No difference Not reported No difference 
Stimulation intensity Not reported Not reported Comparable between awake and asleep groups 
Postoperative clinical outcomes Not reported Not reported No difference 
Perioperative complications Asleep group had lower risk of infection compared to awake group No difference No difference 
Other findings Asleep group required fewer passes per lead compared to awake group Not reported Intracranial air lower in asleep compared to the awake group 
Results
UPDRS III improvement No difference Data suggest a trend toward improved UPDRS III score under awake technique, though statistically insignificant No difference 
Postoperative LEDD No difference No difference No difference 
Adverse events Not reported No difference No difference 
Adverse effects – related to stimulation Stimulation-related effects less in awake versus asleep No difference No difference 
Adverse effects – intracranial hemorrhage Rate of intracranial hemorrhage was lower in asleep group Not reported No difference 
Adverse effects – speech disturbances Not reported Not reported No difference 
Operating time No difference Not reported No difference 
Stimulation intensity Not reported Not reported Comparable between awake and asleep groups 
Postoperative clinical outcomes Not reported Not reported No difference 
Perioperative complications Asleep group had lower risk of infection compared to awake group No difference No difference 
Other findings Asleep group required fewer passes per lead compared to awake group Not reported Intracranial air lower in asleep compared to the awake group 

ICH, intracranial hemorrhage; LEDD, Levadopa equivalent daily dose; UPDRS III, Unified Parkinson’s Disease Rating Scale Part III.

Systematic review of multiple electronic databases was commenced on February 1, 2022: Cochrane Central Register of Controlled trials, Embase, Medline and OVID, Clinicaltrrials.gov and Cochrane library. The last search was conducted on November 25, 2022.

The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement was followed. In addition, references of the included studies were scrutinized for additional studies. Search keywords used alone or in combination included: “Deep Brain Stimulations,” “Anesthesia, General,” “GA,” “LA,” “DBS,” “Awake operation,” “Asleep operation,” “General Anesthesia” were used. The index terms and keywords were explored and truncated according to syntax rules of each database.

We included all published randomized controlled trials (RCTs), prospective and retrospective studies, and case series which compared asleep and awake techniques for patients undergoing DBS for PD. We excluded studies which did not compare outcomes of awake or asleep DBS surgeries for PD, review articles and case reports, and different studies done on the same patient population. Endnotes were used to remove duplicated studies. Two reviewers (A.B.B., S.J.L.) worked independently to select the studies for inclusion in the review and cross-checked the outcome data. The same two reviewers independently extracted and cross-checked the outcome data. Any disagreements were calibrated by the third reviewer (M.L.L.).

Statistics: Assessment of Heterogeneity and Reporting Biases in Meta-Analysis

Data on the variables of interest were extracted from the included studies. Based on Cochrane handbook recommendations, where mean values were not reported, median values were used; and standard deviation, if not reported, was imputed by interquartile range divided by 1.35 [16]. A random-effects meta-analysis was performed on the included studies. A random-effects model, in contrast to a fixed-effects model, does not assume that the relative risk is the same across studies and yields a more conservative estimate of the effect. Heterogeneity between studies was assessed using the Cochran’s Q test and I2 index measure.

I2 describes the percentage of total variation across studies, that is, due to heterogeneity rather than chance. I2 can be readily calculated from basic results obtained from a typical meta-analysis as I2 = 100% (Q – df)/Q, where Q is Cochran’s heterogeneity statistic and df is the degrees of freedom. Negative values of I2 are put equal to zero so that I2 lies between 0% and 100%. A value of 0% indicates no observed heterogeneity, and larger values show increasing heterogeneity [16]. For the qualitative interpretation of heterogeneity, I2 values of at least 40% are usually considered to represent substantial heterogeneity, whereas values of at least 75% indicate considerable heterogeneity. Heterogeneity was considered statistically significant when the p value derived from Cochran’s Q test was <0.1.

Funnel plot was used to assess publication bias in Unified Parkinson’s Disease Rating Scale motor (UPDRS III) outcome and operative complications. Publication bias was not evaluated in the other outcome measures due to lack of power as the number of included studies was less than ten, according to Cochrane handbook recommendations.

The GRADE system was used to give an overall assessment of the quality of evidence relating to the outcomes. Significance level was set at 5%. The meta-analysis was conducted with Review Manager software (RevMan, version 5.3, The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, 2014).

Outcome Measures

Data were extracted on each of the study characteristics, patient demographics, disease duration and patient comorbid conditions. The following outcome measures were analyzed.

  • Clinical effectiveness of DBS: Postoperative UPDRS III score, l-dopa equivalent daily dose (LEDD), and DBS stimulation requirements

The Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (UPDRS) [17] is the gold standard and most frequently used reference scale for PD in clinical settings and scientific trials in PD. It includes four components – mentation (part I), behavior and mood (part II); activities of daily living; motor symptoms (part III); and complications of therapy (part IV). The UPDRS III evaluates speech, facial expression, rigidity, gait, posture, bradykinesia, and tremors. It also includes the Hoehn and Yahr staging for symptom progression of PD. The motor scores are graded on a scale of normal, sight, mild, moderate or severe, with a minimum score of 0 and a maximum score of 108, with a higher score indicating worse motor symptoms. DBS for PD is aimed to benefit the motor component, hence the UPDRS III, which is the motor component of the UPRDS scale is used to assess patient’s perioperatively.

l-dopa is the main pharmacological treatment for PD. However, side effects from l-dopa and its derivatives can limit the doses administered. DBS can help ease motor symptoms and decrease the dosage of l-dopa. As there is variability in medications and dose regimens for PD, a conversion factor is used to generate a total LEDD, calculated as a sum of each parkinsonian medication [18].

DBS stimulation requirements are an important surrogate marker for DBS surgical outcomes. Less than ideal placements of the electrode may indicate a need for higher stimulation voltage or more complex programming in order to achieve the clinical benefit, which can translate to reduce battery efficiency or increased stimulation side effects.

  • Surgical and anesthetic factors: Perioperative surgical and anesthesia complications, number of DBS lead insertions required and operative time

Complications which occurred as a result of surgery or anesthesia in the included papers were reviewed. We classified complications into surgical and anesthetic related complications. For this meta-analysis, surgical complications are defined as “any deviation from the normal postoperative course” [19] and included the following: surgical site infections, stroke, intracranial hemorrhage, hematoma, seizures, pneumocephalus, lead or material dysfunction, lead repositioning, reoperation, revision or failure. Anesthetic related complications [20] included the following: cardiovascular, respiratory (hypoxia, dyspnea, pulmonary embolism, reintubation) complications, hallucinations, confusion, or postoperative delirium.

  • Functional outcomes: Patient’s quality of life, mood, and cognitive measures: PDQ-39, MDRS, and MMSE scores

PDQ-39 was developed by Peto and Jenkinson in 1995 and assesses the health status and quality of life in patients with PD across eight discrete dimensions. The 39 questions cover the domains of daily living, including mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort.

The MDRS is a dementia screening instrument recommended by the Movement Disorders Society Task Force to screen for mild cognitive impairment in PD [21]. It includes dimensions in memory, orientation, judgment, and problem solving, community affairs, hobbies and home affairs and personal care.

Search Results

Our search strategy initially identified 45,316 clinical studies, after excluding duplicate studies. A further 45,065 articles were excluded based on their irrelevancy to our hypothesis and 72 full-text articles were assessed for further eligibility. Of these 72 studies, 1 was excluded as it was not written in the English language, 30 studies comprised of the wrong population and 22 studies had unclear or insufficient data. As a result, 19 studies were included in this review as demonstrated in Figure 1.

Fig. 1.

Flowchart according to the PRISMA statement.

Fig. 1.

Flowchart according to the PRISMA statement.

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This included 3 randomized controlled trials, 14 retrospective studies, and 3 case-controlled studies with comparing arms. A total of 1,990 patients were analyzed, of which 769 patients underwent awake DBS insertion, and 1,221 patients underwent asleep DBS insertion.

The included studies and baseline patient demographics and characteristics of included studies are summarized in Table 2. There was no significant demographical difference between the 2 patient groups for age, disease duration and Hoehn and Yahr (H&Y) stage. The mean age of patients undergoing asleep and awake DBS insertion was 61.0 ± 4.6 and 58.9 ± 9.6 years, respectively. The mean disease duration for asleep and awake patients was 10.97 ± 1.89 and 10.98 ± 2.18 years, respectively. There was no significant difference in the mean H&Y stage the awake and asleep groups at 2.7 ± 0.3 and 2.7 ± 0.3, respectively.

Table 2.

Baseline demographics and characteristics of included articles

Study (year)Study designCountrySample sizeAsleepAwakeAge, mean ± SDMale/femaleDisease duration, mean ± SDComorbidity, mean ± SDH&Y stage, mean ± SD
asleepawakeasleepawakeasleepawakeasleepawakeasleepawake
Gadot et al. [22] (2022) Retrospective with comparison USA 122 52 70 59.0±9.0 61.0±8 40±12 51±19 10.2±3.4 10.7±4.7 NR NR NR NR 
Lee et al. [23] (2022) Retrospective with comparison USA 218 144 (STN: 55 GPi: 89 74 (STN: 51 GPi: 23) 64.2±8.8 64.2±8.1 90±54 53±21 NR NR NR NR NR NR 
Jiang et al. [15] (2021) Retrospective with comparison China 68 35 33 56.3±9.1 56.4±9.2 25±10 * 18±5* 9.20±2.7 9.67±3.26 NR NR 2.4±0.7 2.4±0.5 
Holewijn et al. [13] (2021) RCT American 110 54 56 61.3±7.9 60.0±7.4 38±16 40±16 10.6±5.0 10.8±5.3 NR NR NR NR 
Engelhardt et al. [14] (2020) RCT France 30 20 9 (1 did not undergoDBS) 60.0±7.4* 63.0±8.9* 14±6 6±3 12±7.3* 10±1.48* NR NR NR NR 
Senemmar et al. [24] (2020) Retrospective with comparison Germany 104 80 24 63.0±NR 58.4±NR NR NR 9.2±NR 9.3±NR NR NR 2.6±NR 2.5±NR 
Tsai et al. [4] (2019) Case control with compare arms China (Taiwan) 50 36 14 47.5±9.0 39.6±12.9 15±7 12±2 NR NR NR NR NR NR 
Mirzadeh et al. [25] (2018) Retrospective with comparison USA 323 168 155 NR NR NR NR NR NR NR NR NR NR 
Chen et al. [5] (2018) Retrospective with comparison USA 133 103 (Gpi: 62, STN: 41) 30 (Gpi: 16, STN: 14) 64.0*±8.4* 63.0*±10.6* 73*±30* 19*±11* 8.8*±4.4* 9.5*±8.8* NR NR NR NR 
10 Lefranc et al. [1] (2017) Retrospective France 23 13 10 62.8±7.1 63.1±10 9±13 5±5 12.1±3.5 12.6±3.6 NR NR 2.8±0.6 2.9±0.5 
11 Brodsky et al. [11] (2017) Case control with compare arms Portland 69 30 (STN: 7, Gpi: 23) 39 (STN: 18, Gpi: 21) 63.7±9.8 63.1±7.6 20±10 26±13 NR NR NR NR NR NR 
12 Blasberg et al. [26] (2017) Retrospective with comparison Germany 96 48 48 65.8±1.2 65.5±1.1 33±15 34±14 11.7±0.8 10.9±0.8 3±48 4±49 3.0±0.1 3.0±0.1 
13 Ko et al. [27] (2015) Retrospective with comparison USA 371 324 47 67.0±43.7* 67±23.7* 198±126 35±12 NR NR NR NR NR NR 
14 Saleh et al. [8] (2015) Retrospective with comparison USA 37 14 23 64.0±11.9 60.6±7.0 8±6 13±11 10.9±3.8 11.3±4.9 NR NR NR NR 
15 Nakajima et al. [28] (2010) Retrospective with comparison United Kingdom 82 14 68 56.1±6.5 57.5±7.0 8±6 45±23 13.8±8.1 15.2±8.1 NR NR NR NR 
16 Sutcliffe et al. [9] (2008) Retrospective with comparison United Kingdom 46 26 20 58.0±16.3* 56.3±4.9* 21±5 12±8 8.9±2.7* 10.9±6.6* NR NR NR NR 
17 Yamada et al. [3] (2007) Retrospective with comparison Japan 25 15 10 65.2±7 65.6±8.6 6±9 3±7 11.1±5.0 6.8±2.4 NR NR NR NR 
18 Lefaucheur et al. [6] (2007) RCT United Kingdom 54 N: 30 24 57.7±11.1 61.2±8.1 NR NR 14.0±4.0 14.2±4.8 NR NR NR NR 
19 Maltête et al. [2] (2004) Retrospective with comparison France 30 N: 15 15 59.0±8.0 58.0±6.1 11/4 9/6 13.4±3.7 13.5±2.6 NR NR NR NR 
Overall: frequency/mean (95% CI) 1,991 1,221 769 60.7 (58.4, 63) 60.4 (58, 62.9) 609/329 381/176 10.9 (10, 11.9) 11.2 (10, 12.4) 3/48 4/49 2.7 (2.5, 3) 2.8 (2.4, 3.1) 
Study (year)Study designCountrySample sizeAsleepAwakeAge, mean ± SDMale/femaleDisease duration, mean ± SDComorbidity, mean ± SDH&Y stage, mean ± SD
asleepawakeasleepawakeasleepawakeasleepawakeasleepawake
Gadot et al. [22] (2022) Retrospective with comparison USA 122 52 70 59.0±9.0 61.0±8 40±12 51±19 10.2±3.4 10.7±4.7 NR NR NR NR 
Lee et al. [23] (2022) Retrospective with comparison USA 218 144 (STN: 55 GPi: 89 74 (STN: 51 GPi: 23) 64.2±8.8 64.2±8.1 90±54 53±21 NR NR NR NR NR NR 
Jiang et al. [15] (2021) Retrospective with comparison China 68 35 33 56.3±9.1 56.4±9.2 25±10 * 18±5* 9.20±2.7 9.67±3.26 NR NR 2.4±0.7 2.4±0.5 
Holewijn et al. [13] (2021) RCT American 110 54 56 61.3±7.9 60.0±7.4 38±16 40±16 10.6±5.0 10.8±5.3 NR NR NR NR 
Engelhardt et al. [14] (2020) RCT France 30 20 9 (1 did not undergoDBS) 60.0±7.4* 63.0±8.9* 14±6 6±3 12±7.3* 10±1.48* NR NR NR NR 
Senemmar et al. [24] (2020) Retrospective with comparison Germany 104 80 24 63.0±NR 58.4±NR NR NR 9.2±NR 9.3±NR NR NR 2.6±NR 2.5±NR 
Tsai et al. [4] (2019) Case control with compare arms China (Taiwan) 50 36 14 47.5±9.0 39.6±12.9 15±7 12±2 NR NR NR NR NR NR 
Mirzadeh et al. [25] (2018) Retrospective with comparison USA 323 168 155 NR NR NR NR NR NR NR NR NR NR 
Chen et al. [5] (2018) Retrospective with comparison USA 133 103 (Gpi: 62, STN: 41) 30 (Gpi: 16, STN: 14) 64.0*±8.4* 63.0*±10.6* 73*±30* 19*±11* 8.8*±4.4* 9.5*±8.8* NR NR NR NR 
10 Lefranc et al. [1] (2017) Retrospective France 23 13 10 62.8±7.1 63.1±10 9±13 5±5 12.1±3.5 12.6±3.6 NR NR 2.8±0.6 2.9±0.5 
11 Brodsky et al. [11] (2017) Case control with compare arms Portland 69 30 (STN: 7, Gpi: 23) 39 (STN: 18, Gpi: 21) 63.7±9.8 63.1±7.6 20±10 26±13 NR NR NR NR NR NR 
12 Blasberg et al. [26] (2017) Retrospective with comparison Germany 96 48 48 65.8±1.2 65.5±1.1 33±15 34±14 11.7±0.8 10.9±0.8 3±48 4±49 3.0±0.1 3.0±0.1 
13 Ko et al. [27] (2015) Retrospective with comparison USA 371 324 47 67.0±43.7* 67±23.7* 198±126 35±12 NR NR NR NR NR NR 
14 Saleh et al. [8] (2015) Retrospective with comparison USA 37 14 23 64.0±11.9 60.6±7.0 8±6 13±11 10.9±3.8 11.3±4.9 NR NR NR NR 
15 Nakajima et al. [28] (2010) Retrospective with comparison United Kingdom 82 14 68 56.1±6.5 57.5±7.0 8±6 45±23 13.8±8.1 15.2±8.1 NR NR NR NR 
16 Sutcliffe et al. [9] (2008) Retrospective with comparison United Kingdom 46 26 20 58.0±16.3* 56.3±4.9* 21±5 12±8 8.9±2.7* 10.9±6.6* NR NR NR NR 
17 Yamada et al. [3] (2007) Retrospective with comparison Japan 25 15 10 65.2±7 65.6±8.6 6±9 3±7 11.1±5.0 6.8±2.4 NR NR NR NR 
18 Lefaucheur et al. [6] (2007) RCT United Kingdom 54 N: 30 24 57.7±11.1 61.2±8.1 NR NR 14.0±4.0 14.2±4.8 NR NR NR NR 
19 Maltête et al. [2] (2004) Retrospective with comparison France 30 N: 15 15 59.0±8.0 58.0±6.1 11/4 9/6 13.4±3.7 13.5±2.6 NR NR NR NR 
Overall: frequency/mean (95% CI) 1,991 1,221 769 60.7 (58.4, 63) 60.4 (58, 62.9) 609/329 381/176 10.9 (10, 11.9) 11.2 (10, 12.4) 3/48 4/49 2.7 (2.5, 3) 2.8 (2.4, 3.1) 

DBS, deep brain stimulation; N, number; GPi, Globus pallidus internus; H&Y, Hoehn and Yar stage; SD, standard deviation; STN, subthalamic nucleus; RCT, randomized controlled trial; NR, not recorded.

*Calculated value.

Assessment of Risk of Bias of the Included Studies

The Cochrane Collaboration’s tool was used to assess the risk of bias for each study. Six domains – selection, performance, detection, attrition, reporting, and other bias were assessed.

Each domain was judged to have high (red), low (green), or unclear risk (yellow) of bias for each item. Results of the assessment are presented in Figure 2. Other than the randomized controlled trials which had low risk of selection bias, majority of the studies had a high risk of bias.

Fig. 2.

Risk of bias summary showing the risk of bias for each study. Green plus sign = low risk; red minus sign = high risk; yellow question mark = unclear risk.

Fig. 2.

Risk of bias summary showing the risk of bias for each study. Green plus sign = low risk; red minus sign = high risk; yellow question mark = unclear risk.

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Outcome Measures

Clinical Effectiveness

In all the included studies, the UPDRS III score was assessed postoperatively when the patients were off all their PD medications and had DBS stimulation switched on. This thus assesses the therapeutic effect of DBS only on the patient. Our analysis was standardized and evaluated between 3 months and 1 year after surgery, except for Tsai [4], which recorded UPDRS scores 5 years postoperatively. Our meta-analysis comparing awake versus asleep effect on postoperative UPDRS III score in 567 asleep patients and 432 awake patients did not show a significant difference between the two groups (mean difference 1.71, 95% CI [−0.04, 3.46]; p = 0.06; I2 = 32%, p = 0.12).

The LEDDs were evaluated between 6 months and 1 year in all studies except for Tsai [4], which was similarly performed at 5 years. There was significant heterogeneity in the postoperative LEDDs. Comparison between postoperative LEDD in 809 patients (448 in the asleep group and 316 in the awake group) demonstrated no significant difference in postoperative LEDD in the awake and asleep groups (mean difference [−11.77], 95% CI [−89.07–65.54]; p = 0.06; I2 = 43%, p = 0.07). The requirements for DBS stimulation to exert clinical effect post-surgery in 278 patients in the sleep group were compared to 127 patients in the awake group which also demonstrated no significant difference (mean difference 0.12, 95% CI [−0.03–0.28]; p = 0.13; I2 = 0%, p = 0.71) (Fig. 3).

Fig. 3.

Forest and funnel plots of between asleep and awake DBS surgery in studies evaluating postoperative UPDRS III score; postoperative LEDD and DBS stimulation requirements.

Fig. 3.

Forest and funnel plots of between asleep and awake DBS surgery in studies evaluating postoperative UPDRS III score; postoperative LEDD and DBS stimulation requirements.

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Surgical and Anesthesia Factors

A total of 1,123 patients (605 from the awake group, 518 from the asleep group) from 15 studies were included in our analysis for surgical complications up till 1 year postoperatively. There was no significant difference in surgical related complications (odds ratio 1.18, 95% CI: 0.63–2.22; p = 0.61; I2 = 27%; p = 0.17).

Anesthesia complications were assessed in the immediate postoperative period. A total of 1,006 patients (553 in the asleep group and 453 in the awake group) from 14 studies were included in the analysis for anesthetic related complications. There were a total of 30 events in the asleep group and 25 events in the awake group (odds ratio 0.85, 95% CI: 0.44–1.62; p = 0.63; I2 = 0%; p = 0.74). There was no significant difference in anesthetic-related complications between asleep and awake groups.

The risk of intraoperative events including tractal hemorrhage has been associated with corresponding increase in lead insertions [10]. A total of 186 patients (100 in the asleep group, 86 in the awake group) in three studies were included. There was otherwise no significant difference reported between the awake and asleep groups on the number of lead insertions required during surgery in the included three studies (mean difference [−0.22], 95% CI [−0.72 – 0.27]; p 0.37; I2 39%, p = 0.19).

With regards to operative time, a total of 1,205 patients (760 in the asleep group, 445 in the awake group) in 10 studies were included. Operative time for the asleep group was significantly less than the awake group (mean difference [−28.47], 95% CI [−50.56 to −6.39]; p = 0.01, I2 = 84%, p = <0.00001) There was, however, significant heterogeneity with the I2 of 84%. This could be due to some studies including the implantable pulse generator insertion time as part of their total operative times (Fig. 4).

Fig. 4.

Forest plots of asleep and awake DBS surgery in studies evaluating surgical complications; anesthesia complications; number of lead insertions; operative time.

Fig. 4.

Forest plots of asleep and awake DBS surgery in studies evaluating surgical complications; anesthesia complications; number of lead insertions; operative time.

Close modal

There were a total of 3 mortalities in our patients included in this meta-analysis – two in the awake group [5, 9] and one in the asleep group. One death in the awake group [9] occurred from an intraoperative hematoma developing at the track site of a permanent electrode. We did not attribute the other two deaths to be directly related to the surgery as they occurred two and 4 months postoperatively from unrelated causes [5, 13].

Patient’s Quality of Life, Mood, and Cognitive Measures

In the analysis for quality of life, three studies reported the postoperative PDQ-39 scores at 6 months. There was no significant difference between 82 patients in the asleep group compared to 71 patients in the awake group (mean difference [−2.12], 95% CI [−6.55 – 2.30]; p = 0.35; I2 = 0%; p = 0.68).

Three studies with a total of 143 patients (of which 77 were asleep and 66 awake) reported post-DBS MDRS scores at 6 months to 1 year. The asleep and awake groups had a 2.32% and 3.38% improvement in MDRS scores from baseline. There was no significant change in the mean improvement of MDRS scores between the two groups (mean difference 0.2, 95% CI [−1.45 – 1.95]; p = 0.82; I2 = 0%; p = 0.54).

Two studies with 104 patients (57 in the asleep group, 47 in the awake group) used the MMSE 6 months postoperatively [30] and at 5 years [12] to assess cognitive function. There was no significant difference in postoperative MMSE (mean difference 0.26, 95% CI [−0.69 – 1.20]; p = 0.59; I2 0%; p = 0.34) (Fig. 5).

Fig. 5.

Forest plots of between asleep and awake DBS surgery in studies evaluating PDQ-39 scores; MDRS scores; MMSE scores.

Fig. 5.

Forest plots of between asleep and awake DBS surgery in studies evaluating PDQ-39 scores; MDRS scores; MMSE scores.

Close modal

In 2021, the World Health Organization reported that the prevalence of PD has doubled in the last 25 years and that the resultant disability and death from the disease is increasing faster than for any other neurological disorder [29]. In addition to l-dopa, DBS has been shown to improve motor outcomes and quality of life for patients with PD with proven long-term cost-effectiveness [30].

As previously mentioned, the traditional gold standard for DBS surgery is performed in an awake patient with the intraoperative adjuncts of neurophysiological monitoring via MER and clinical testing to determine optimal lead placement [9, 31, 32]. Stimulation effects such as the therapeutic threshold and side effect threshold can also be identified and leads can be tested and adjusted intraoperatively. Our meta-analyses demonstrate that there was no significant difference in clinical and functional outcomes. However, this methodology requires the patient to remain awake and conscious during the entire DBS electrode insertion procedure, which can range from 3:50 to 8:45 h [33]. This may pose a challenge to patients who are already in an off-medication state and adds considerable discomfort and anxiety related to their surgery [11]. Furthermore, there are patients who may not be able to tolerate awake surgery due to their severe dystonia, chorea, or anxiety [6, 34]. In addition, it is reported that up to 40% of patients undergoing awake DBS experienced uncomfortable or occasionally unbearable pain, especially during the stereotactic frame placement or drilling of burr holes, despite ongoing sedation [34]. Intraoperative clinical testing can also become unreliable as patients become fatigued with the prolonged surgical duration. It may then be difficult for the surgical team to determine if clinical improvement is due to the current or previous electrode effect [9, 10].

An alternative image-guided approach to DBS whereby the surgery is performed on asleep patients has been described by several institutions [3, 28, 35] and have appeared to achieve comparable results [10]. To clarify, asleep DBS may be performed with the aid of intraoperative fluoroscopy, magnetic resonance imaging (ClearPoint), O-arm or Ceretom, all of which for the purpose of this study are assumed to be equivalent [7]. Suboptimal targeting [36] using pure imaging techniques [3, 37, 38] may also be supplanted with intraoperative MER localizations [9, 32]. In our meta-analysis, MER during asleep DBS was employed in the majority (12 out of 16) of our included studies. With the exception of Engelhart et al. [14], who employed their institution specific probabilistic stereotactic coordinate targeting, the remaining groups employed image-guided asleep DBS only. The basis of MER lies in the characteristic discharge pattern of single neurons in various components of the basal ganglia and thalamus that allows for identification of the location of microelectrode in real-time as it advances along the planned trajectory to the target. Anesthesia agents such as benzodiazepines, barbiturates, etomidate, and inhalational agents should be avoided as they potentiate the inhibitory actions of GABA within the basal ganglia and thus affect the neurophysiological signals during DBS surgeries [39, 40]. Although propofol potentiates the response to GABA in a dose-dependent manner and reduces excitability of neurons, patients who had propofol infusion with a bispectral index (BIS) target of 60–65 displayed firing patterns of the STN similar to awake patients [41] and had no clinically relevant difference between awake and asleep groups [6]. Otherwise, both ketamine and dexmedetomidine have shown minimal effect on MER recordings when discontinued for at least 20 min prior [40, 42]. Thus, modification of anesthetic protocols and reduction of anesthetic depth during surgery is suggested to facilitate intraoperative MER testing to be performed on asleep patients [15, 43]. In addition, although most of the included studies did not report their electrode repositioning rate, there was 3 leads in the asleep group that required repositioning [4, 5, 8] as compared to one in the awake group [8].

Understandably, there are also concerns regarding the risk of GA causing postoperative delirium, drowsiness, nausea, or vomiting for patients with undergoing DBS insertion [10, 43, 44]. Patients with PD suffer from sialorrhea, laryngeal, and pharyngeal muscle dyskinesia, which contributes to the risk of retained secretions and aspiration [45], leading to respiratory complications. Hemodynamic instability can also develop rapidly due to the patient’s poor physiological reserves. Despite the concerns with GA [43], our study did not reveal any significant difference in anesthetic or surgical complications between the awake and asleep groups. Asleep DBS may provide better operative conditions for the surgical and anesthetic team as the patient is completely paralyzed, airway is protected and the intracranial pressure is well controlled [44]. The asleep patient also obviates the need for constant communication which reduces distraction [46] for the operating and anesthesia teams [9]. In our study, asleep DBS was shown to have significantly reduced operative times. Prolonged operative times are known to be associated with increased risk of perioperative complications in neurosurgical patients including infections, pulmonary embolism, and pneumonia [47]. Asleep DBS may therefore possibly confer a more rapid postoperative recovery and avails DBS for patient who would otherwise find it difficult or impossible to tolerate awake surgery due to their anxiety, severe off symptoms such as painful dystonia, communication problems or breathing difficulties [34]. This can potentially translate into increased accessibility of DBS, reduced surgical anxiety and improved patient comfort [6, 7].

The strengths of the meta-analysis are only as robust as the quality of articles from which they are derived. The included articles were mostly retrospective, with considerable heterogeneity in the postoperative follow-up times, ranging from 3 months to 5 years in some of the studies. Only three studies could be included for analyses of quality of life and neurocognitive outcomes. In addition, we have only included studies which directly compared asleep and awake techniques, and thus not all studies for DBS insertion in PD patients were included.

It should also be highlighted that the asleep DBS studies included in our analysis are from highly specialized centers with considerable experience with intraoperative imaging and, in general, both awake and asleep techniques. Thus, their results may not be generalizable to all DBS centers that may have less experience with either approach.

With the advent of newer technology such as better imaging and surgical techniques, newer drugs and monitoring devices, there is likely to have narrowing differences in outcomes between awake or asleep DBS. What would therefore be more important is meticulous planning and vigilance at all stages of the surgical and anesthesia processes; consider the patient’s comfort and clinical status as well as the operative team’s familiarity with the procedure to ensure seamless transition and care.

An ethics statement is not applicable because this study is based exclusively on published literature.

The authors have no conflicts of interest to declare.

No funding was required for this study.

M.L.L. and A.B.B.Z.: conception of study, acquisition, analysis, interpretation of data, and manuscript draft. S.J.L.: acquisition, analysis, interpretation of data, and manuscript draft. E.S.S.: analysis, interpretation of data, and manuscript draft and review. W.L.: analysis, interpretation of data, and manuscript review. M.M.T., W.H.N., and T.G.W.: conception of study, analysis, interpretation of data, and manuscript review. K.R.W.: conception of study, acquisition, analysis, interpretation of data, and manuscript draft and review.

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.

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