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Stress, Anxiety, and Depression Associated With Awake Craniotomy: A Systematic Review. BACKGROUND: Awake craniotomy (AC) enables real-time monitoring of cortical and subcortical functions when lesions are in eloquent brain areas. AC patients are exposed to various preoperative, intraoperative, and postoperative stressors, which might affect their mental health. OBJECTIVE: To conduct a systematic review to better understand stress, anxiety, and depression in AC patients. METHODS: PubMed, Scopus, and Web of Science databases were searched from January 1, 2000, to April 20, 2022, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline. RESULTS: Four hundred forty-seven records were identified that fit our inclusion and exclusion criteria for screening. Overall, 24 articles consisting of 1450 patients from 13 countries were included. Sixteen studies (66.7%) were prospective, whereas 8 articles (33.3%) were retrospective. Studies evaluated stress, anxiety, and depression during different phases of AC. Twenty-two studies (91.7%) were conducted on adults, and 2 studies were on pediatrics (8.3 %). Glioma was the most common AC treatment with 615 patients (42.4%). Awake-awake-awake and asleep-awake-asleep were the most common protocols, each used in 4 studies, respectively (16.7%). Anxiety was the most common psychological outcome evaluated in 19 studies (79.2%). The visual analog scale and self-developed questionnaire by the authors (each n = 5, 20.8%) were the most frequently tools used. Twenty-three studies (95.8%) concluded that AC does not increase stress, anxiety, and/or depression in AC patients. One study (4.2%) identified younger age associated with panic attack. CONCLUSION: In experienced hands, AC does not cause an increase in stress, anxiety, and depression; however, the psychiatric impact of AC should not be underestimated.

PubMed, Scopus, and Web of Sciences databases were searched from January 1, 2000, to April 20, 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.45 Details of search terms for each database are presented in Supplementary Table S1, http://links.lww.com/NEU/D453. Three authors (M.M., M.S.M., and S.A.) screened for relevant articles through the reference lists of selected articles. Eligibility criteria were (1) original articles published between January 1, 2000, and April 20, 2022; (2) English only; (3) focused on the psychiatric aspects of AC, such as “stress,” “anxiety,” or “depression” and by using psychiatric tools and evaluations; and (4) involved human subjects only. The exclusion criteria were (1) case report articles with ≤4 subjects; (2) qualitative psychiatric studies; (3) studies which inferred stress, anxiety, and depression from nonpsychiatric parameters (ie, heart rate, blood pressure, and blood components); and (4) studies which investigated neurosurgical interventions other than AC, for example, burr holes in deep brain stimulation.46,47 Extracted data are presented in Tables 1, 2, and 3 and Supplementary Tables S2, http://links.lww.com/NEU/D454; S3, http://links.lww.com/NEU/D455; and S4, http://links.lww.com/NEU/D456. All calculations were performed on Microsoft Excel (version 2016; Microsoft). Summary of Studies Characteristics AC, awake craniotomy; GA, general anesthesia; HGG, high-grade glioma; LGG, low-grade glioma; NA, not applicable; NS, not specified.

Extracted data are presented in Tables 1, 2, and 3 and Supplementary Tables S2, http://links.lww.com/NEU/D454; S3, http://links.lww.com/NEU/D455; and S4, http://links.lww.com/NEU/D456. All calculations were performed on Microsoft Excel (version 2016; Microsoft). Summary of Studies Characteristics AC, awake craniotomy; GA, general anesthesia; HGG, high-grade glioma; LGG, low-grade glioma; NA, not applicable; NS, not specified. This study reported an age range 17-72 years, which overlaps with the children's range determined in this review; however, because the mean age reported was 50 years, it was considered an adult study. This study did not specify the full protocol. Details of Psychiatric Evaluations from Studies Reviewed AC, awake craniotomy; APAIS, Amsterdam Preoperative Anxiety and Information Scale; BDI, Beck depression inventory; DSM, diagnostic and statistical manual of mental disorders; GAD, generalized anxiety disorder; HADS, hospital anxiety and depression scale; NA, not applicable; NS, not specified; PASS, pain anxiety symptoms scale; PCL-C, post-traumatic stress disorder checklist civilian version; PCLS; post-traumatic stress disorder checklist scale; PHQ, patient health questionnaire; PSS, perceived stress scale; PTSD, post-traumatic stress disorder; STAI, state-trait anxiety inventory; VAS, visual analogue scale. Main Outcomes and Conclusions from Each Study Reviewed

AC, awake craniotomy; APAIS, Amsterdam Preoperative Anxiety and Information Scale; BDI, Beck depression inventory; DSM, diagnostic and statistical manual of mental disorders; GAD, generalized anxiety disorder; HADS, hospital anxiety and depression scale; NA, not applicable; NS, not specified; PASS, pain anxiety symptoms scale; PCL-C, post-traumatic stress disorder checklist civilian version; PCLS; post-traumatic stress disorder checklist scale; PHQ, patient health questionnaire; PSS, perceived stress scale; PTSD, post-traumatic stress disorder; STAI, state-trait anxiety inventory; VAS, visual analogue scale. Main Outcomes and Conclusions from Each Study Reviewed AC, awake craniotomy; BDI, Beck depression inventory; GA, general anesthesia; HADS, hospital anxiety and depression scale; PASS, pain anxiety symptoms scale; PSS, perceived stress scale; PTSD, post-traumatic stress disorder; VAS, visual analog scale.

PubMed, Scopus, and Web of Sciences databases were searched from January 1, 2000, to April 20, 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.45 Details of search terms for each database are presented in Supplementary Table S1, http://links.lww.com/NEU/D453. Three authors (M.M., M.S.M., and S.A.) screened for relevant articles through the reference lists of selected articles.

Eligibility criteria were (1) original articles published between January 1, 2000, and April 20, 2022; (2) English only; (3) focused on the psychiatric aspects of AC, such as “stress,” “anxiety,” or “depression” and by using psychiatric tools and evaluations; and (4) involved human subjects only. The exclusion criteria were (1) case report articles with ≤4 subjects; (2) qualitative psychiatric studies; (3) studies which inferred stress, anxiety, and depression from nonpsychiatric parameters (ie, heart rate, blood pressure, and blood components); and (4) studies which investigated neurosurgical interventions other than AC, for example, burr holes in deep brain stimulation.46,47

Our search yielded 440 results: 55 from PubMed, 283 from Scopus, and 102 from Web of Science. After screening reference lists, 7 records were added. Duplicate records (n = 157) were removed, the remaining studies (n = 290) were screened based on their titles and abstracts, and nonrelevant studies (n = 151) were removed. The remaining articles (n = 139) were then fully read for eligibility. Overall, 24 studies met the eligibility criteria for the final review (Figure). Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart demonstrating search, screen, inclusion, and exclusion process for this study. An overview of studies included is presented in Supplementary Table S2, http://links.lww.com/NEU/D454.5,32,43,48-68 Of 24 studies included, 17 (70.8%) were from Europe,5,32,48-56,58,60,61,63,65,68 4 (16.7%) from Asia,43,59,66,67 and 3 (12.5%) from North America.57,62,64 Sixteen studies (66.7%) were conducted prospectively, and 8 studies (33.3%) were retrospective. Twenty-one articles (87.5%) focused on brain tumors only,5,32,43,48-53,55,57-68 whereas the other 3 studies (12.5%) had a mixture of lesions.54,56,64

4 (16.7%) from Asia,43,59,66,67 and 3 (12.5%) from North America.57,62,64 Sixteen studies (66.7%) were conducted prospectively, and 8 studies (33.3%) were retrospective. Twenty-one articles (87.5%) focused on brain tumors only,5,32,43,48-53,55,57-68 whereas the other 3 studies (12.5%) had a mixture of lesions.54,56,64 Although AC is a well-established surgical approach, considerable differences exist in surgery, anesthesia, and stimulation techniques used in different centers depending on multiple factors, such as team preference, lesion type and location, patient characteristics, and comorbidities.6,69 The most common protocols were the awake-awake-awake5,51,54,57 and the asleep-awake-asleep protocols,43,60,63,64 each reported in 4 studies (16.7%; Table 1). Studies which used the awake-awake-awake approach measured acute stress and anxiety,51 post-traumatic stress disorder (PTSD), anxiety alone,57 and anxiety and depression.5 By contrast, studies which used asleep-awake-asleep measured anxiety48,55,60; combination of stress, anxiety, and depression63,64; or combination of PTSD, anxiety, and depression.43 Eight studies (33.3%) did not specify the anesthetic protocol used.49,50,52,53,59,62,65,67

, anxiety alone,57 and anxiety and depression.5 By contrast, studies which used asleep-awake-asleep measured anxiety48,55,60; combination of stress, anxiety, and depression63,64; or combination of PTSD, anxiety, and depression.43 Eight studies (33.3%) did not specify the anesthetic protocol used.49,50,52,53,59,62,65,67 The shortest follow-up was 3 to 7 days,51 and the longest follow-up was 13 months.68 Postoperative anxiety was not significantly different at the 1-month (P = .99) and 6-month (P = .26) follow-up compared with preoperative anxiety.43 Similarly, postoperative depression at the 1-month (P = .79) and 6-month follow-up (P = .95) was not statistically different compared with preoperative depression levels.43 Eight studies (33.3%) did not specify the length of their follow-up.32,48-50,52,57,59,67

(P = .26) follow-up compared with preoperative anxiety.43 Similarly, postoperative depression at the 1-month (P = .79) and 6-month follow-up (P = .95) was not statistically different compared with preoperative depression levels.43 Eight studies (33.3%) did not specify the length of their follow-up.32,48-50,52,57,59,67 One thousand four hundred fifty patients were included in this systematic review (Table 1). Kamata et al66 contained the largest sample size with 405 patients (27.9%), followed by van Ark et al60 with 272 patients (18.8%). The smallest sample size was in Riquin et al58 and Stalnacke et al,68 each with 7 patients (0.483%). Apart from 2 studies (8.3%) which were conducted on pediatrics,58,63 all other articles (91.7%) had adult patient populations (Supplementary Table S3, http://links.lww.com/NEU/D455). In total, 1426 patients (98.3%) were adults, and 24 patients (1.7%) were pediatrics. Multiple factors, including concerns about tolerance, case complexity, a higher risk of postoperative neurocognitive deficits, and a lower frequency of lesions in eloquent areas, make AC less widely used in children.70-73

om/NEU/D455). In total, 1426 patients (98.3%) were adults, and 24 patients (1.7%) were pediatrics. Multiple factors, including concerns about tolerance, case complexity, a higher risk of postoperative neurocognitive deficits, and a lower frequency of lesions in eloquent areas, make AC less widely used in children.70-73 Five studies (20.8%) compared stress, anxiety, and depression among patients undergoing AC and GA (Supplementary Table S3, http://links.lww.com/NEU/D455).49,50,60,65,67 Hol et al49 reported that both preoperative and 12 hours postoperative anxiety levels were higher in the GA group compared with AC (P < .05). Supporting these findings, another retrospective study comparing AC with GA found that preoperative anxiety was significantly lower in the AC group compared with GA (P = .020).60 By contrast, Staub-Bartelt et al65 did not find significantly different preoperative anxiety levels in AC compared with GA patients (P = .630). In another article, both the GA and AC groups had significantly reduced postoperative stress (P < .001) and anxiety (P = .013) compared with corresponding preoperative levels.50 In the same study, the AC group had a significantly lower 12 hours postoperative anxiety when compared with the GA group (P = .009). Van Ark et al60 showed that a significant reduction in postoperative anxiety compared with the preoperative level was only seen in the GA group (P < .001) and not in the AC group (P = .612). By comparing 37 AC patients (38.5%) with 59 GA patients (61.4%), Bakhshi et al67 did not find a statistically significant difference in mean postoperative depression levels between groups (P = .06), concluding that AC tumor resection does not increase postoperative depression compared with tumor resection under GA.

2). By comparing 37 AC patients (38.5%) with 59 GA patients (61.4%), Bakhshi et al67 did not find a statistically significant difference in mean postoperative depression levels between groups (P = .06), concluding that AC tumor resection does not increase postoperative depression compared with tumor resection under GA. The lowest reported mean age among AC patients was 15 years,63 and the highest was 60 years (Table 1).62 Patients younger than 50 years had a higher level of preoperative anxiety compared with older patients (P = .037).5 Another study reported that intraoperative anxiety was higher in patients younger than 60 years (P = .0145).55 By contrast, Hejrati et al61 did not find any differences in stress, anxiety, and depression levels of young (younger than 35 years) and old (50 years or older) patients. Van Ark et al60 also did not find any significant correlation between anxiety and age before and after surgery. Four studies (16.7%) did not specify the mean age.52,53,58,60 A caveat was that the definition of young age varied between different studies. For example, Beez et al55 considered younger than 60 years as young, whereas Ruis et al5 considered younger than 55 years as young based on the median of their sample. Moreover, patients younger than 39 years were considered young by Kamata et al,66 whereas Milian et al54 did not define the young age cohort.

t studies. For example, Beez et al55 considered younger than 60 years as young, whereas Ruis et al5 considered younger than 55 years as young based on the median of their sample. Moreover, patients younger than 39 years were considered young by Kamata et al,66 whereas Milian et al54 did not define the young age cohort. Ruis et al5 reported that female patients had more preoperative anxiety compared with male patients (P = .005). Similarly, Rahmani et al43 reported that female patients had significantly higher preoperative anxiety (P = .001) and depression (P = .001). In addition, Beez et al55 found female patients had significantly higher intraoperative anxiety compared with male patients (P = .0103). Van Ark et al60 found that only preoperative anxiety (P = .032), and not postoperative anxiety (P = .87), was significantly elevated in female patients. Three studies (12.5) did not specify sex of patients (Supplementary Table S3, http://links.lww.com/NEU/D455).58,60,62 Glioma was the most represented lesion type, corresponding to 615 patients (42.4%; Table 1). Eight studies (33.3%) did not specify the lesion type.48-50,58,59,61,63,66 Rahmani et al43 reported that patients with glioblastoma had a higher preoperative anxiety level compared with patients with anaplastic astrocytoma (P = .017).

was the most represented lesion type, corresponding to 615 patients (42.4%; Table 1). Eight studies (33.3%) did not specify the lesion type.48-50,58,59,61,63,66 Rahmani et al43 reported that patients with glioblastoma had a higher preoperative anxiety level compared with patients with anaplastic astrocytoma (P = .017). Nineteen studies (79.2%) evaluated anxiety as one of their psychiatric outcomes,5,43,48-53,55,57,59-66,68 and 10 studies (41.7%) measured stress or PTSD (Table 2).32,43,49-51,54,56,58,63,64 Four studies (16.7%) assessed depression as part of their psychiatric evaluations.43,63,64,67 Only 3 studies (12.5%) evaluated PTSD.43,54,58

tudies (79.2%) evaluated anxiety as one of their psychiatric outcomes,5,43,48-53,55,57,59-66,68 and 10 studies (41.7%) measured stress or PTSD (Table 2).32,43,49-51,54,56,58,63,64 Four studies (16.7%) assessed depression as part of their psychiatric evaluations.43,63,64,67 Only 3 studies (12.5%) evaluated PTSD.43,54,58 The visual analog scale74 and questionnaires developed by investigators were the most common tools used in the articles reviewed (Table 2). Five studies (20.8%) used visual analog scale,49,50,55,57,62 and another 5 studies (20.8%) used a self-developed questionnaire.32,48,54,56,60 Among those who used a self-developed questionnaire, Whittle et al48 developed a 10-item questionnaire asking patients about their memories of operation, sensation experience, level of fear, relaxation, comfort, adequacy of preoperative explanation, awake phase length, their views on the number of staff present, and recommendations for change. Milian et al54 developed a questionnaire inspired by DSM-IV to ask patients about core aspects of PTSD during the initial phase of the surgery and the AC phase. A questionnaire containing 11 items was designed with the help of a psychiatrist to complement other assessment tools.32 Their questionnaire asked patients about their sensations, memories, feeling, sense of time, pleasant, and unpleasant experiences. The 19-item questionnaire by Joswig et al56 asked patients about their comfort, experience, instructions received, and memories after AC. The questionnaire by Van Ark et al60 asked patients about the quality and quantity of their memories and experience.

es, feeling, sense of time, pleasant, and unpleasant experiences. The 19-item questionnaire by Joswig et al56 asked patients about their comfort, experience, instructions received, and memories after AC. The questionnaire by Van Ark et al60 asked patients about the quality and quantity of their memories and experience. Sixteen studies (66.7%) conducted psychiatric evaluations during the preoperative phase,5,43,49-53,58-65,68 and 18 studies (75.0%) performed postoperative psychiatric evaluation (Table 2).32,43,48-51,53,54,56-59,61,63,64,67,68 Only 5 studies (20.8%) used intraoperative psychiatric evaluation.52,55,57,62,66 Eleven studies (45.8%) did psychiatric evaluations at preoperative and postoperative phases of AC.43,49-51,53,58-61,63,68 Not all studies investigated stress, anxiety, and depression in patients undergoing AC in follow-up. Hejrati et al61 demonstrated that AC does not affect stress, anxiety, and depression at the 3-month follow-up. Similarly, Rahmani et al43 found that stress and anxiety did not significantly change at the 6-month follow-up, although the mean anxiety had a decreasing trend.

ression in patients undergoing AC in follow-up. Hejrati et al61 demonstrated that AC does not affect stress, anxiety, and depression at the 3-month follow-up. Similarly, Rahmani et al43 found that stress and anxiety did not significantly change at the 6-month follow-up, although the mean anxiety had a decreasing trend. Fourteen studies (58.3%) specified psychiatric support and coping strategies provided for AC patients (Table 2).5,32,43,48,51,54-66 Neurosurgeons and anesthetists were among the team involved in counseling and psychiatric support for patients in 6 studies (25.0%) each, respectively,32,43,48,51,55,56,66 followed by psychiatrists/psychologists/neuropsychologists in 5 studies (20.8%).43,51,58,63,64 Psychiatric support was provided by nurses in 4 studies (16.7%).48,55,62,66 Some coping mechanisms provided were mentioned. For example, Riquin et al58 offered meetings with previous pediatric patients to share their experience of AC procedures. They also arranged a preoperative visit to the operating room and meetings with the entire team to familiarize patients with the environment. A day before the surgery, a simulation of the awake situation was provided, and the entire procedure was practiced with the patient.65 Kamata et al66 reported that intensive preoperative preparations were provided, and patients were shown a short movie of the entire procedure to familiarize them with AC. Staub-Bartelt et al65 reported that all patients were offered preoperative psycho-oncological support at hospitalization, and 15 patients (27.8%) accepted the offer. Another study reported that stress management techniques were offered by a psychologist or a speech-language pathologist.64 In 1 study, 22 patients (88.0%) reported the care and support received by the staff as the most positive aspect of their experience during AC.51 Ten studies (41.7%) did not specify the psychiatric support provided.5,49,50,52,53,57,59,61,67,68

techniques were offered by a psychologist or a speech-language pathologist.64 In 1 study, 22 patients (88.0%) reported the care and support received by the staff as the most positive aspect of their experience during AC.51 Ten studies (41.7%) did not specify the psychiatric support provided.5,49,50,52,53,57,59,61,67,68 Eight studies (33.3%) reported intraoperative seizure as the most common complication (Table 2).32,51,55-57,60,63,66 An intraoperative seizure occurred in 13.6% of patients reported by Beez et al55 with a mean duration of 12 seconds (range, 2-30 seconds), mainly in patients with a history of epilepsy; however, all the surgeries were successfully continued as planned. In another study, 5 patients (12.0%) experienced intraoperative focal seizures, which were resolved after irrigating the brain with cold saline, while 7 patients (16.0%) had nausea and 5 patients (12.0%) experienced vomiting.32 However, all their procedures continued. Fourteen studies (58.3%) did not specify intraoperative complications.5,43,49,50,52-54,58,59,61,62,65,67,68

An overview of studies included is presented in Supplementary Table S2, http://links.lww.com/NEU/D454.5,32,43,48-68 Of 24 studies included, 17 (70.8%) were from Europe,5,32,48-56,58,60,61,63,65,68 4 (16.7%) from Asia,43,59,66,67 and 3 (12.5%) from North America.57,62,64 Sixteen studies (66.7%) were conducted prospectively, and 8 studies (33.3%) were retrospective. Twenty-one articles (87.5%) focused on brain tumors only,5,32,43,48-53,55,57-68 whereas the other 3 studies (12.5%) had a mixture of lesions.54,56,64

Although AC is a well-established surgical approach, considerable differences exist in surgery, anesthesia, and stimulation techniques used in different centers depending on multiple factors, such as team preference, lesion type and location, patient characteristics, and comorbidities.6,69 The most common protocols were the awake-awake-awake5,51,54,57 and the asleep-awake-asleep protocols,43,60,63,64 each reported in 4 studies (16.7%; Table 1). Studies which used the awake-awake-awake approach measured acute stress and anxiety,51 post-traumatic stress disorder (PTSD), anxiety alone,57 and anxiety and depression.5 By contrast, studies which used asleep-awake-asleep measured anxiety48,55,60; combination of stress, anxiety, and depression63,64; or combination of PTSD, anxiety, and depression.43 Eight studies (33.3%) did not specify the anesthetic protocol used.49,50,52,53,59,62,65,67 The shortest follow-up was 3 to 7 days,51 and the longest follow-up was 13 months.68 Postoperative anxiety was not significantly different at the 1-month (P = .99) and 6-month (P = .26) follow-up compared with preoperative anxiety.43 Similarly, postoperative depression at the 1-month (P = .79) and 6-month follow-up (P = .95) was not statistically different compared with preoperative depression levels.43 Eight studies (33.3%) did not specify the length of their follow-up.32,48-50,52,57,59,67

One thousand four hundred fifty patients were included in this systematic review (Table 1). Kamata et al66 contained the largest sample size with 405 patients (27.9%), followed by van Ark et al60 with 272 patients (18.8%). The smallest sample size was in Riquin et al58 and Stalnacke et al,68 each with 7 patients (0.483%). Apart from 2 studies (8.3%) which were conducted on pediatrics,58,63 all other articles (91.7%) had adult patient populations (Supplementary Table S3, http://links.lww.com/NEU/D455). In total, 1426 patients (98.3%) were adults, and 24 patients (1.7%) were pediatrics. Multiple factors, including concerns about tolerance, case complexity, a higher risk of postoperative neurocognitive deficits, and a lower frequency of lesions in eloquent areas, make AC less widely used in children.70-73

Five studies (20.8%) compared stress, anxiety, and depression among patients undergoing AC and GA (Supplementary Table S3, http://links.lww.com/NEU/D455).49,50,60,65,67 Hol et al49 reported that both preoperative and 12 hours postoperative anxiety levels were higher in the GA group compared with AC (P < .05). Supporting these findings, another retrospective study comparing AC with GA found that preoperative anxiety was significantly lower in the AC group compared with GA (P = .020).60 By contrast, Staub-Bartelt et al65 did not find significantly different preoperative anxiety levels in AC compared with GA patients (P = .630). In another article, both the GA and AC groups had significantly reduced postoperative stress (P < .001) and anxiety (P = .013) compared with corresponding preoperative levels.50 In the same study, the AC group had a significantly lower 12 hours postoperative anxiety when compared with the GA group (P = .009). Van Ark et al60 showed that a significant reduction in postoperative anxiety compared with the preoperative level was only seen in the GA group (P < .001) and not in the AC group (P = .612). By comparing 37 AC patients (38.5%) with 59 GA patients (61.4%), Bakhshi et al67 did not find a statistically significant difference in mean postoperative depression levels between groups (P = .06), concluding that AC tumor resection does not increase postoperative depression compared with tumor resection under GA.

The lowest reported mean age among AC patients was 15 years,63 and the highest was 60 years (Table 1).62 Patients younger than 50 years had a higher level of preoperative anxiety compared with older patients (P = .037).5 Another study reported that intraoperative anxiety was higher in patients younger than 60 years (P = .0145).55 By contrast, Hejrati et al61 did not find any differences in stress, anxiety, and depression levels of young (younger than 35 years) and old (50 years or older) patients. Van Ark et al60 also did not find any significant correlation between anxiety and age before and after surgery. Four studies (16.7%) did not specify the mean age.52,53,58,60 A caveat was that the definition of young age varied between different studies. For example, Beez et al55 considered younger than 60 years as young, whereas Ruis et al5 considered younger than 55 years as young based on the median of their sample. Moreover, patients younger than 39 years were considered young by Kamata et al,66 whereas Milian et al54 did not define the young age cohort.

t studies. For example, Beez et al55 considered younger than 60 years as young, whereas Ruis et al5 considered younger than 55 years as young based on the median of their sample. Moreover, patients younger than 39 years were considered young by Kamata et al,66 whereas Milian et al54 did not define the young age cohort. Ruis et al5 reported that female patients had more preoperative anxiety compared with male patients (P = .005). Similarly, Rahmani et al43 reported that female patients had significantly higher preoperative anxiety (P = .001) and depression (P = .001). In addition, Beez et al55 found female patients had significantly higher intraoperative anxiety compared with male patients (P = .0103). Van Ark et al60 found that only preoperative anxiety (P = .032), and not postoperative anxiety (P = .87), was significantly elevated in female patients. Three studies (12.5) did not specify sex of patients (Supplementary Table S3, http://links.lww.com/NEU/D455).58,60,62

Glioma was the most represented lesion type, corresponding to 615 patients (42.4%; Table 1). Eight studies (33.3%) did not specify the lesion type.48-50,58,59,61,63,66 Rahmani et al43 reported that patients with glioblastoma had a higher preoperative anxiety level compared with patients with anaplastic astrocytoma (P = .017).

Nineteen studies (79.2%) evaluated anxiety as one of their psychiatric outcomes,5,43,48-53,55,57,59-66,68 and 10 studies (41.7%) measured stress or PTSD (Table 2).32,43,49-51,54,56,58,63,64 Four studies (16.7%) assessed depression as part of their psychiatric evaluations.43,63,64,67 Only 3 studies (12.5%) evaluated PTSD.43,54,58

Eight studies (33.3%) reported intraoperative seizure as the most common complication (Table 2).32,51,55-57,60,63,66 An intraoperative seizure occurred in 13.6% of patients reported by Beez et al55 with a mean duration of 12 seconds (range, 2-30 seconds), mainly in patients with a history of epilepsy; however, all the surgeries were successfully continued as planned. In another study, 5 patients (12.0%) experienced intraoperative focal seizures, which were resolved after irrigating the brain with cold saline, while 7 patients (16.0%) had nausea and 5 patients (12.0%) experienced vomiting.32 However, all their procedures continued. Fourteen studies (58.3%) did not specify intraoperative complications.5,43,49,50,52-54,58,59,61,62,65,67,68

AC is a well-established surgical intervention for pathologies in eloquent brain areas that maximize patient outcomes and minimize neurological deficits. Several studies have shown evidence for positive patient perception and tolerance of AC.33,75-78 AC requires multidisciplinary teamwork including, but not limited to, neurosurgeons, neurologists, psychiatrists, psychologists, neurophysiologists, speech and physical therapists, and specialized nurses.79 Multiple biopsychosocial factors can influence mental health,80 and psychiatric outcomes after neurosurgery have been proposed to affect the quality of life and even the 5-year survival rate.81 The studies reviewed here showed that AC can be well-tolerated by patients and does not result in elevated stress, anxiety, and depression (Table 3). There is no assessment tool designed specifically for evaluating psychiatric outcomes among AC patients. Therefore, different centers used different psychiatric assessment tools, including questionnaires developed by different groups. Such heterogeneity can affect the findings. Therefore, a robust consensus psychiatric assessment tool needs to be established to specifically examine stress, anxiety, and depression in patients undergoing AC.

nt centers used different psychiatric assessment tools, including questionnaires developed by different groups. Such heterogeneity can affect the findings. Therefore, a robust consensus psychiatric assessment tool needs to be established to specifically examine stress, anxiety, and depression in patients undergoing AC. Different studies assessed stress, anxiety, and depression at various phases of AC, namely preoperative, intraoperative, and postoperative, with some studies focusing on a single phase and others assessing multiple phases. Patients can be exposed to multiple factors at different phases of AC. Some studies showed that postoperative stress and anxiety of patients undergoing AC could be significantly different compared with the GA group. Anticipating surgery can be a stress factor for patients,58 and some findings indicate that preoperative anxiety is lower among AC patients. Female sex and younger age were risk factors for a high level of anxiety in AC in some studies, consistent with observations from other neurosurgical procedures.82-84 Multiple aspects of the operation, such as the length of the operation, the extent of the blood loss, lesion size and localization, craniotomy size, and the duration of hospitalization, can impact stress, anxiety, and depression. Future studies are required to address the importance of such variables in stress, anxiety, and depression in AC.

operation, such as the length of the operation, the extent of the blood loss, lesion size and localization, craniotomy size, and the duration of hospitalization, can impact stress, anxiety, and depression. Future studies are required to address the importance of such variables in stress, anxiety, and depression in AC. Psychological support at follow-up can improve stress, anxiety, and depression in patients who undergo AC. Such support can be tailored to individual patients by identifying risk factors at the preoperative stage that can make patients susceptible to elevated stress, anxiety, and depression. Although no randomized data exist, it is likely that such support delivered by teams experienced in performing AC is critical in reducing psychiatric morbidity in patients. Such programs, in general, are more commonly integrated within AC protocols than GA craniotomy routines and might explain the lower psychiatric burden reported with the former in some comparative studies. These AC paradigms translated to GA surgeries might therefore directly benefit patients undergoing craniotomy under GA.

programs, in general, are more commonly integrated within AC protocols than GA craniotomy routines and might explain the lower psychiatric burden reported with the former in some comparative studies. These AC paradigms translated to GA surgeries might therefore directly benefit patients undergoing craniotomy under GA. Our review was limited to articles published in English, and there was heterogeneity in the articles reviewed. Eight studies with a total of 830 patients (57.2%) were retrospective, which can affect the level of the evidence available and the strength of analyses. Furthermore, the number of patients in each study and data collection period varied widely. No study evaluated stress, anxiety, and depression at all preoperative, intraoperative, and postoperative phases of AC. Therefore, future studies are required to evaluate psychiatric outcomes during all AC phases. Other factors such as personality traits, coping strategies provided, and cognitive functions can also influence the level of stress and anxiety, making their comparison more challenging. In addition, the studies reviewed had different inclusion and exclusion criteria, which can introduce selection bias. Some studies had a long and varied interval between the time of surgery and survey, with potential recall biases. Future studies are required to compare the overall survival and progression-free survival of patients undergoing AC with different anesthetic approaches. Despite such limitations, the current review can be a useful addition to help understand mental health in neurosurgical procedures.

Our review was limited to articles published in English, and there was heterogeneity in the articles reviewed. Eight studies with a total of 830 patients (57.2%) were retrospective, which can affect the level of the evidence available and the strength of analyses. Furthermore, the number of patients in each study and data collection period varied widely. No study evaluated stress, anxiety, and depression at all preoperative, intraoperative, and postoperative phases of AC. Therefore, future studies are required to evaluate psychiatric outcomes during all AC phases. Other factors such as personality traits, coping strategies provided, and cognitive functions can also influence the level of stress and anxiety, making their comparison more challenging. In addition, the studies reviewed had different inclusion and exclusion criteria, which can introduce selection bias. Some studies had a long and varied interval between the time of surgery and survey, with potential recall biases. Future studies are required to compare the overall survival and progression-free survival of patients undergoing AC with different anesthetic approaches. Despite such limitations, the current review can be a useful addition to help understand mental health in neurosurgical procedures.

Based on the current report, AC can be regarded as a safe neurosurgical approach which does not cause an increase in the stress, anxiety, and depression of patients. The benefits of AC outweigh its risks, and potential psychiatric challenges are manageable by experienced teams with good psychiatric support for patients. Comprehensive psychiatric assessments should be performed during preoperative, intraoperative, and postoperative phases of AC, using specific tools designed to improve patient outcomes. Future large-scale, multicenter studies with a long-term follow-up are required to address some of the outstanding questions.