Awake Craniotomy in Africa: A Scoping Review of Literature and Proposed Solutions to Tackle Challenges

BACKGROUND: Awake craniotomy (AC) is a common neurosurgical procedure for the resection of lesions in eloquent brain areas, which has the advantage of avoiding general anesthesia to reduce associated complications and costs. A significant resource limitation in low- and middle-income countries constrains the usage of AC. OBJECTIVE: To review the published literature on AC in African countries, identify challenges, and propose pragmatic solutions by practicing neurosurgeons in Africa. METHODS: We conducted a scoping review under Preferred Reporting Items for Systematic Reviews and Meta-Analysis-Scoping Review guidelines across 3 databases (PubMed, Scopus, and Web of Science). English articles investigating AC in Africa were included. RESULTS: Nineteen studies consisting of 396 patients were included. Egypt was the most represented country with 8 studies (42.1%), followed by Nigeria with 6 records (31.6%). Glioma was the most common lesion type, corresponding to 120 of 396 patients (30.3%), followed by epilepsy in 71 patients (17.9%). Awake-awake-awake was the most common protocol used in 7 studies (36.8%). Sixteen studies (84.2%) contained adult patients. The youngest reported AC patient was 11 years old, whereas the oldest one was 92. Nine studies (47.4%) reported infrastructure limitations for performing AC, including the lack of funding, intraoperative monitoring equipment, imaging, medications, and limited human resources. CONCLUSION: Despite many constraints, AC is being safely performed in low-resource settings. International collaborations among centers are a move forward, but adequate resources and management are essential to make AC an accessible procedure in many more African neurosurgical centers.

R ecent global estimates indicate that although more than 22.6 million people suffer from disorders and injuries requiring the expertise of a neurosurgeon yearly, about 5 million individuals are unable to undergo the required neurosurgical treatments because of multiple factors, including resource limitations. 1 This is particularly the case in low-and middle-income countries (LMIC) in Africa, where neurosurgical procedures are mainly performed under general anesthesia (GA), a more resource-intensive undertaking usually requiring postoperative hospitalization and rehabilitation. 2 It is an unfortunate global economic reality that worldwide disparities in neurosurgical care can and unfortunately do result in preventable disabilities and deaths in many LMIC, 1 a fact further affirmed by the revelation that neurological diseases are the leading cause of disability-adjusted life-years and the second leading cause of global mortality. 3 Awake craniotomy (AC) is becoming a common neurosurgical procedure used in many advanced neurosurgical units to aid real-time mapping of eloquent brain areas to maximize lesion resection while minimizing postoperative neurological complications, and its use is beneficial within LMIC. 4 AC is used for various indications, including epilepsy, tumors, arteriovenous malformations, aneurysms, and deep brain stimulation. [5][6][7] Patients are sedated while awake for parts or all of the surgery duration, thereby bypassing some demands and complications often associated with GA, which includes endotracheal intubation, and the need for ventilators, arterial lines, catheters, and postoperative intensive care, 8 and yielding better patient outcomes when compared with GA. 9,10 Furthermore, AC can lower the long-term costs associated with neurosurgical procedures by reducing the hospitalization time, decreasing the requirement for extensive monitoring devices, shortening the recovery time after discharge, reducing morbidity, and preserving patients' employment because of low postoperative neurological deficits. [11][12][13][14] Intuitively, these benefits should merit AC's use as a feasible procedure to be more frequently deployed in the LMIC just as it is regularly performed in the developed countries. 15,16 However, several factors have acted as barriers that make its use relatively uncommon in LMIC. [17][18][19] One of the questions that must be addressed in the discourse surrounding AC concerns itself with the limited data published from LMIC, especially in the Eastern, Central, and most of Western Africa, in treating patients. In this scoping review, we explore the present state of AC in Africa and identify key barriers along the way. We then propose practical solutions to overcome some of the challenges by relying on the meticulous analysis of some of the continent's practicing neurosurgeons. To our knowledge, this is the first review that accomplishes a synthesis of the published peer-reviewed literature on AC in Africa with the aforementioned goals in mind.

Search Strategy
This scoping review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis-Scoping Review (PRISMA-ScR). 20 A population (African patients), concept (AC), and context (limited-resource setting) were established. PubMed, Scopus, and Web of Science databases were searched from inception to June 20th 2022 for relevant articles. Details of the search terms for each database are available in Supplementary Table 1, http://links.lww.com/NEU/D710. We did not use Boolean terms for Africa or individual countries to avoid the possibility of excluding relevant articles. Instead, we screened the affiliation of the listed authors for a more comprehensive search strategy. Articles were selected initially if at least 1 author was from Africa. Full-text articles were then read to establish whether the investigation was conducted in Africa.

Inclusion and Exclusion Criteria
Articles were included if they met the following criteria: (1) original peer-reviewed articles with a digital objective identifier, (2) English only, (3) AC used as a neurosurgical procedure in Africa, (4) provided sufficient quantitative data and were accessible on databases used, and (5) articles involving human subjects only. The exclusion criteria were (1) articles that aggregated AC data on African and non-African countries without differentiating the Africa sources, (2) sufficient extractable data were not provided, and (3) studies that investigated neurosurgical interventions other than AC (eg, minicraniotomy 21
Two studies (10.5%) compared AC with GA, 22,29 and demonstrated better patient outcomes for AC patients compared with GA. For example, although 14 patients (70%) were admitted into intensive care unit (ICU) in the GA group (5 seizures, 4 brain  edema, 3 delayed recoveries, and 2 agitations), only 2 AC patients (10%) had postoperative complications (1 seizure and 1 brain edema) requiring ICU care (P = .0004). 22 The same group showed the hospitalization length was reduced from 8.15 ± 6.5 days in the GA cohort to 3.8 ± 4.15 days in the AC group (P = .05). 22 Furthermore, another study illustrated the advantage of AC over GA by reporting less permanent postoperative neurological deficits in AC patients (5%) vs those undergoing GA (8.3%) (P = .59) 29 (Table 1).
Eloquent area mapping is an integral part of the AC program, influencing the extent of resection and, thereby, prognosis. 53,54 Direct electrical stimulation (DES) is the gold standard for identifying eloquent areas to maximize lesion resection and reduce new neurological deficits. [55][56][57] Relying solely on preoperative clinical information to determine the eloquent areas is associated with significant morbidity. 58 Only 6 studies (31.6%) used DES. [26][27][28][29]39,40 Others relied on continuous monitoring of patients' speech and motor functions, 22,36,37 because of a lack of stimulator devices, which is a common problem in LMIC 13 (Supplementary Table 5, http://links.lww.com/NEU/D714).
Conversion to GA can complicate AC, rendering the procedure a failure, for many reasons, including uncontrolled intraoperative seizure and lack of patient tolerance. 59

Constraints to AC in Low-Resource Centers
Lack of appropriate infrastructure, shortage of surgical, nursing, and anesthesia staff, prolonged waiting time, and the quality of training have been considered some of the constraints of neurosurgical care. 61 The safety and feasibility of AC in low-resource settings where modern and expensive technologies, such as functional and intraoperative MRI, intraoperative cortical mapping, and electrophysiology, are not available can add significant challenges. 22 Nine studies (47.4%) reported infrastructure limitations as an obstacle to performing AC operations, 22,26,28,[30][31][32][33][34]39 with 1 study noting that the lack of head pins at their hospital hindered AC procedures 30 (Table 3).
Optimal anesthesia techniques should achieve analgesia and sedation while preventing side effects such as nausea, vomiting, and seizures. 62 Lack of access to special anesthetic medications, including remifentanil and dexmedetomidine, equipment required for neurophysiological monitoring and brain mapping, and the presence of an experienced team of neurosurgeons and anesthetists are some of the other limiting factors for carrying out AC in LMIC. 28 Balogun et al 31 in Nigeria did not have access to histology and molecular profiling facilities; therefore, they were unable to specify the tumor subtype with certainty. Furthermore, they reported financial constraints for postoperative MRIs delaying the radiation therapy initiation to the tumor bed, and wholebrain radiation therapy since health care in their setting is predominantly financed "out-of-pocket" by the patient. 31 Benyaich et al, 39 in their study conducted in Morocco, specified that lack of functional MRI and tractography, ultrasonic surgical aspirator, neuronavigation, intraoperative imaging, other neuromonitoring devices, and human resources as the main barriers at their center.
Safe AC requires the cooperation of the neurosurgical and anesthesia teams to maintain the patient awake during the resection, and monitor the patient's responses and development of new neurological deficits. 62 Although other professionals may not be required at all times, Benyaich et al 39 reported that neuropsychologists, speech therapists, and neurophysiologists were present for the first 2 procedures (10%) during the establishment of the programs in Morocco with the help of an experienced team from Europe. Thereafter, adaptations to the AC program were required to suit accessible resources, and only neurosurgeons and anesthesiologists with episodic participation of a neurologist with neuropsychological training were involved in the AC procedures. 39

Cultural and Religious Considerations
Local cultural values and expectations have been shown to influence patients' health-seeking behavior. 31,63 For example, Benyaich et al 39 reported a mean duration of 17 ± 4.9 months from the onset of symptoms to admission to the neurosurgical department, attributing such delays to cultural belief, such as the association of seizure-as it was the most common presenting symptom in 70% of their cases-with a social stigma of being possessed by demonical power. Furthermore, patients' preference to consult traditional healers without any medical training can also delay medical consultation. 64 Even when patients seek medical

DISCUSSION
AC with brain mapping is a safe and cost-effective neurosurgical procedure enabling maximal lesion resection in eloquent brain areas while minimizing neurological complications, thereby providing an excellent alternative to craniotomy under GA. 55,[66][67][68] One of the advantages of AC over GA is the shorter hospitalization to save the hospital and human resources, particularly in low-resource settings, reduce postoperative complications, such as infection, and result in increased patient satisfaction. 8,66,[69][70][71][72] Although admission to ICU after brain surgery is a routine procedure in developed countries, which enables close monitoring and early detection of complications, establishing and maintaining neuro-ICU can be resource-intensive and costly in low-resource settings. 31,[73][74][75][76][77] If stringent patient inclusion criteria, including preoperative functional status of the patient, tumor location, brain edema, social support at home, and accessibility to hospital for readmission, are considered, AC patients can be discharged on the same or next day. 69,78,79 Early discharge can be more suitable for both patients and the healthcare system. 78,80-83 AC can also accelerate return to work to enable patients to continue with their employment, 84 given that social support for disabled patients is scarce in Africa. 39 It should be noted that postsurgical care at home and in the community requires reliable infrastructure and appropriate living conditions, which are not consistently available in Africa. 66 For example, ambulances are largely absent in low-resource settings, and patients rely primarily on family and caregivers for transportation to and from the hospital, narrowing the spectrum of patients who can be offered outpatient surgical procedures. 31 Therefore, we emphasize that biopsychosocial conditions should be considered when selecting patients for AC.
AC is a complex procedure relying on intraoperative brain mapping, imaging and neuromonitoring, specific anesthetic medications, and trained teams, which are not readily available in LMIC. [85][86][87][88] Intraoperative functional mapping during AC can reduce the incidence of postoperative deficits from 13%-to 27.5% to less than 2%. 89 Nevertheless, DES of cortical and subcortical areas to identify eloquent areas is not feasible in all centers, especially those in Africa, because of a lack of infrastructure and financial constraints. Recent studies also suggest the assessment of intraoperative neurophysiological parameters such as electrocorticography and electromyography, as well as using artificial intelligence, augmented and virtual reality in AC. [90][91][92][93] The utilization of such equipment and technologies increases the cost of the procedure and is not readily available in many neurosurgery departments in Africa. 39,94,95 However, such technological resources are not absolutely necessary. 18 Best patient outcomes are achieved in neurosurgical centers with a multidisciplinary team with extensive experience in AC. 4,15,53,96 Successful AC programs require a team of neurosurgeons, anesthesiologists, neurologists, neurophysiologists, neuropsychiatrists, specialized nurses, and speech therapists during preoperative, intraoperative, and postoperative phases of the procedure. 4 Constraints in human resources have prompted neurosurgical colleagues from Africa to adapt AC programs with minimum staff where the intraoperative patient evaluation is safely conducted by neurosurgeons and anesthesiologists alone, with the occasional participation of neurologists who have neuropsychological training. 95 Knowledge transfer can be used to initiate AC practice with minimum requirements. Enhancing global collaboration between centers with experience in performing AC in highincome countries is required to train competent staff and transfer knowledge for the sustainable establishment of AC centers, followed by supporting equipment required for safely performing operations. An example of the global effort to train teams needed to initiate AC in LMIC was reported in 6 neurosurgical centers in Nigeria, Ghana, Indonesia, and China. 13 In-person visits and establishing partnerships can be supported longitudinally by internet-based content between neurosurgical centers experienced in AC and those in Africa. 18,[97][98][99] This can be sustained by knowledge transfer and collaboration within the continent between centers more experienced in AC with those that plan to initiate such programs.
Africa is a vast continent comprising 54 countries; however, AC studies included in this review were from 5 countries (9.26%) only. Although such findings can highlight the disparity that exists within the continent, an alternative explanation can be the lack of peer-reviewed publications on AC from African centers that were not represented.
Based on the current findings as well as our experience of performing AC in LMIC, we highlight challenges associated with AC in Africa and propose pragmatic solutions to overcome them. We believe implementing these solutions can facilitate the usage of AC in different hospitals across Africa (Table 4). Furthermore, the challenges and magnitude of work that needs to be done by each Ministry of Health and neurosurgeons in representative African countries to initiate and sustain AC as a safe undertaking are illustrated in Figures 3 and 4.

Limitations
Our scoping review is subject to some limitations. Reviewed papers were published in English, and there was heterogeneity in the articles reviewed. Ten studies (52.6%) included in this review, with a total of 113 patients (28.5%), were retrospective, which can affect the level of the evidence available and the strength of analyses. In addition, the number of patients in each study and the data collection period varied widely. Furthermore, studies included were from 5 African countries, representing only 9.26% of African countries. A multicenter study investigating challenges associated with AC in all African countries is recommended. Despite such limitations, the current review can be a useful addition to understanding the state of neurosurgery and AC in Africa.

CONCLUSION
Despite the existence of various constraints to its full uptake, the current review suggests a very encouraging prospect for the feasibility of AC in Africa because the absence of infrastructure has not prevented AC from being performed in many of the LMIC therein. Although the lack of technologies such as DES and neuroimaging devices can be considered a hindrance, they should not prevent neurosurgical centers from the uptake of AC. Similarly, patients in Africa should not be denied the benefits of AC procedures. Although encouraging, various challenges exist in practicing AC in Africa. More resources and training should be allocated to reduce disparity in neurosurgical care in Africa. Failure to address such gaps in neurosurgical treatment can result in wider disparities between developed and LMIC. Other low-resource neurosurgical centers in Africa are encouraged to safely incorporate AC into their neurosurgery programs. The goal should be to foster skills required to sustain AC within the host institutions and develop the next generation of neurosurgeons to change the paradigm.

Funding
This study did not receive any funding or financial support.