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Surgical Neurology 71 (2009) 621–625www.surgicalneurology-online.com

Historical Vignette

The history of awake craniotomy for brain tumorand its spread into Asia

Julius July, MDa,b, Pirjo Manninen, MD, FRCPCc, Jacob Lai, MD, FRCPCc,Zhenhai Yao, MD, PhD, FRCPCc, Mark Bernstein, MD, MHSc, FRCPCa,⁎

aDivision of Neurosurgery, University Health Network, Toronto Western Hospital, Toronto, Ontario, Canada M5T 2S8bDepartment of Neurosurgery, Siloam Lippo Karawaci Hospital, Jl. Siloam No. 6 Lippo Karawaci 1600, Tanggerang, Indonesia

cDepartment of Anesthesia, University Health Network, Toronto Western Hospital, Toronto, Ontario, Canada

Received 11 May 2007; accepted 17 December 2007

Abstract In ancient times, awake craniotomy was used for trepanation to treat seizures and remove a variety of

Abbreviations: FINeurological SurgeryWFNS, World Federa

* Corresponding aE-mail address: m

0090-3019/$ – see frodoi:10.1016/j.surneu.2

morbid conditions or even to permit the escape of evil air. In modern times, this technique wasinitially used for removal of epileptic foci with simultaneous application of brain mapping withelectrical current. Further developments brought this technique into use for resection of tumorsinvolving functional cortex. Recently, awake craniotomy has been described as an approach forremoval of supratentorial tumors nonselectively, regardless of the involvement of eloquent cortex. Ithas been used in North America since the 1980s, then Europe, and recently has spread into Asia. Itsspread to Asia could have significant impact based on the large population of patients and the lowresource utilization associated with awake craniotomy.© 2009 Elsevier Inc. All rights reserved.

Keywords: Asia; Awake craniotomy; Brain tumor; History of neurosurgery

1. The evolution of brain mapping

The idea of awake craniotomy for tumor surgery arosefrom its use for epilepsy surgery. It is known fromarcheological findings that in ancient times, thousands ofyears ago, patients were treated for seizures by trepanation ofthe skull [21,28]. Seizures are a common clinical presenta-tion of brain tumor in adults; and therefore, some of theseancient trepanations must have been done in patientsharboring brain tumors. The surgery was also done tocorrect morbid conditions of the skull like contusion orfracture, or to permit the escape of evil air [14]. The first

ENS, Foundation for International Education in; NIMS, Nizam's Institute of Medical Sciences;tion of Neurosurgical Societies.uthor.arkbernstein@uhn.on.ca (M. Bernstein).

nt matter © 2009 Elsevier Inc. All rights reserved.007.12.022

documentation of awake craniotomy in “modern” times wasto treat epilepsy in the early 17th century [28].

The poor results of trepanation drove physicians andscientists to explore the brain and try to define the seizuresource. Hughlings Jackson, who did an extensive study offocal epilepsy between 1864 and 1870, predicted that an areaexisted in the cerebral cortex that governed isolated move-ments [24]. This was verified by Fritsch and Hitzig in 1870,who for the first time were able to elicit movements of theextremities in animals by means of electrical stimulation onthe cerebral cortex [15].

The first concept of brain mapping with electricalstimulation in humans was generated by Bartholow in 1874[5]. He used an electrode to stimulate the cerebral cortexthrough a skull defect resulting from the osseous infiltrationof an epithelioma. A decade later in 1886, Horsley, whosestudies of animals gave him an excellent understanding of thehuman cortex, and his colleague Jackson applied electricalstimulation to localize the thumb area and decided to excise

622 J. July et al. / Surgical Neurology 71 (2009) 621–625

the area because it was the source of the seizure [22]. Jacksondemonstrated that in focal epilepsy an area could be found onthe cerebral cortex, which would give rise to the seizure. Theexcision of this area, which he called the primary spasmiccenter, was usually followed by a cessation of the attacks.From that time on, electrical stimulation to localize the motorcortex and seizure foci became quite popular.

In the late 1920s, Wilder Penfield was trying to treatpatients with intractable epilepsy [34]. He also applied mildelectric current to map the brain. Before an epileptic seizure,he knew patients experienced an aura, a warning that aseizure is about to occur. He thought that if he could provokethis aura with mild electric current on the brain, then he couldlocate the source of the seizure activity and could potentiallyremove or destroy that bit of tissue. While patients were fullyconscious at craniotomy, he used a thyratron stimulator withunilateral or bipolar electrodes consisting of a platinum wirein a glass holder [29,31]. He rigorously documented all hisintraoperative findings [30-33,36]. He stated that the patientmust be conscious and alert during the electrical stimulationso the patient could warn the surgeon about the aura, motorweakness, or sensory change. His technique was oftensuccessful and reproducible, becoming accepted worldwidefor epilepsy surgery. He also applied awake craniotomy tosome patients with brain tumors, notably his own sister [34].

2. Anesthetic considerations

One of the first large studies describing the anestheticexperience with awake craniotomy was published by Archeret al in 1988 [2]. They described their experience with 347awake craniotomies for cortical resection for epilepsy, usinglocal analgesia and intravenous fentanyl and droperidol. In1992, Silbergeld et al introduced the use of propofol, whichoffers the advantages of being a short-acting sedative withantiemetic and amnestic properties in sedative doses[20,40,43]. There now exists considerable variation in theanesthetic techniques for “awake craniotomy,” ranging fromthe “asleep-awake-asleep” technique, with or without the useof an airway, to those using monitored anesthesia care orconscious sedation [7,16,19,23,27,38].

Propofol and, more recently, remifentanil have beenfrequently used [7,19,27].Midazolam is also popular becauseof its anxiolyic and amnestic properties [17]. Low doses ofmidazolam (0.075 mg/kg) do not affect the ventilatoryresponse to carbon dioxide, suggesting that clinicallysignificant respiratory depression is unlikely at that doserange [35]. In addition, it raises seizure threshold [13] andoffers an extra margin of safety when local anesthetic is used.

3. Awake craniotomy for tumor

Many hemispheric glial and metastatic tumors arelocated within or adjacent to functional areas such asmotor cortex, speech area, and sensory cortex. It has beenshown that functional cortex and subcortical white matter

may be located within the tumor or adjacent infiltrated brain[42]. Using brain mapping techniques for brain tumor surgerywas a logical step from its use in epilepsy surgery and startedto be more widely used for this purpose within the last2 decades [25]. It was used to identify regions of languagerepresentation in the dominant cerebral hemisphere and themotor cortex in either hemisphere. This technique allowsintraoperative mapping to delineate any eloquent cortex andits relationshipwith the tumor and facilitates finding the safesttranscortical route to the tumor and more aggressive tumorresection while minimizing morbidity by preserving func-tional tissue [6].

Another large series of patients treated with awakecraniotomy for brain tumor surgery was published in 1999;200 cases operated over 7 years were reported [44]. Thesame group has recently described their experience in morethan 600 tumor patients [39], which is to our knowledge thelargest such series in the literature. Useful data have arisensuch as the observation that positive mapping was associatedwith a 5% risk of neurologic worsening, whereas negativemapping was associated with 1.8% incidence of patientssustaining neurologic worsening. At the same time, awakecraniotomy for brain tumor also became more and morepopular in other centers [12,37]. For more than 20 years, thistechnique has been shown to be relatively safe, simple, andwell-tolerated by patients.

The avoidance of general anesthesia and its associatedinvasive monitoring could potentially decrease postoperativemedical morbidity and shorten the length of hospital stay; sothat recently, this technique has actually been used foroutpatient craniotomy for brain tumor resection [8-10]. Ofnote is that one small randomized study actually reportedhigher blood loss, more neurologic deficit, and less degree ofcytoreduction in patients undergoing awake craniotomy fortumors in eloquent cortex [18].

4. Spread into Asia

In the late 1990s, several case reports of awakecraniotomy were published in Asia, although most of themwere reported in local neurosurgery journals. Kumabe et al in1997 reported the case of a young man with a brain tumor inthe right motor cortex who was operated in TohokuUniversity Hospital, Sendai, Japan, under propofol anesthe-sia [26]. There are scattered reports of other hospitals andinstitutions in Asia implementing awake craniotomy.

In India, surgeons at Hinduja hospital in Mumbaiperformed its first awake craniotomy in November 1998on a 32-year-old man [11]. Clearly, awake craniotomieshave been done in Delhi in reasonable numbers, culminatingin the admirable performance of a randomized study,although its results are somewhat discordant with theexperience of those teams with larger series [18]. TheNizam's Institute of Medical Sciences in Hyderabad, India,in August 2000 performed its first awake craniotomy on a29-year-old man with a left posterior frontal brain tumor [4].

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In Thailand, Shiriraj Hospital in Bangkok began perform-ing in September 2000 Thailand's first series of awakecraniotomy and functional brain mapping surgeries [41]. InSingapore awake craniotomy with bipolar cortical mappinghas been used successfully and a small series was recentlypublished supporting the advantages of this technique [27].

In Indonesia, through Foundation for InternationalEducation in Neurological Surgery, one of the volunteerneurosurgeons introduced awake craniotomy techniques inNovember 2003. The FIENS collaborates with the WorldFederation of Neurosurgical Societies to address the criticallack of trained neurosurgeons in the developing world [1].The first awake craniotomy in Indonesia for brain tumor wasperformed in Hasan Sadikin Hospital, Bandung. The patientwas a 23-year-old man with a right frontal high-gradeglioma. Since then, this technique has been performedregularly in Bandung and was brought to Cirebon in October2004 and Siloam Hospital, Lippo Karawaci Tangerang, nearJakarta, in December 2005. To the author's knowledgeawake craniotomy is not being performed in Vietnam,Cambodia, Laos, or the Philippines.

In China, as recently as March 2007, awake craniotomywas introduced through collaboration with the University ofToronto. Several awake craniotomies for brain tumor wereperformed at 2 hospitals: Xinxiang Medical College, FirstAffiliated Hospital, Weihui, in Henan Province and XiamenUniversity, Zhongshan Hospital, Xiamen, Fujian Province. Itshould be noted that in China and some other Asian centersproper equipment for cortical mapping is not available sosome patients are benefiting from avoiding a generalanesthetic and invasive monitoring but are not obtainingthe benefit of localization of functionally important cortex.

5. Summary

The above cited cases do not represent an exhaustive listof awake craniotomy activity in Asia—they are experienceswe could find using PubMed and Google searches and/or ofwhich we have direct personal knowledge. We believe thatthe spread of awake craniotomy to Asia, specifically SouthAsia, Southeast Asia, and China, could have a major impacton patient care and resource utilization. These countries arehome to more than half the planet's population and, ingeneral, have less access to health care resources than Japan,Europe, Australia and New Zealand, and North America.Based on data from the Association of National Census andStatistics Directors of America, Asia, and the Pacific, Japan'spopulation in 2005 was 120 million, China's population in2005 was 1308 million, India's population in 2001 was 1028million, Indonesia's population in 2000 was 205 million, andThailand's population in 2000 was 62 million. All thesecountries in total account for 70% of the Asian population [3]and almost half the population on the planet.

Most neurosurgeons who routinely use awake craniotomyfor resection of brain tumor believe that it may enhancethe ability to maximally resect the tumor, which seems

intuitively like an appropriate goal to many surgeons and tomany patients, despite the lack of powerful evidence in favorof this approach for gliomas. Regarding the economicperspective, this procedure may decrease resource utilizationrelated to decreased use of invasive monitoring, shorteroperating room times, and decreased length of stay inhospital postoperatively [8-10,39,44]. All these reasons alsofavor its use in the developing world, where availability ofresources is an ongoing challenge.

Awake craniotomy appears to be well tolerated bypatients and perhaps even allows them a greater measureof control and involvement in their care. There is a shortlearning curve for this procedure for all members of the team—surgeons, anesthetists, nurses, and, of course, patients[45]. There may be cultural differences across the globe inpatients' acceptance of this procedure; but if neurosurgeonsand anesthetists are willing to embrace it, they will gainconfidence that will be transmitted to their patients. We havepersonally observed this firsthand in Indonesia and China.We believe that awake craniotomy could well be used morefrequently and broadly by neurosurgeons to the benefit oftheir patients in all parts of the globe and to the fiscal benefitof complex health care delivery systems.

6. Conclusion

The evolution of awake craniotomy from the ancientpractice of trepanation to modern image-guided surgery withbrain mapping has provided critical insights into the surgicaltreatment of brain tumors. Its spread to Asia could have apositive impact for many patients and for resource-challenged health care systems.

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July et al describe the history of awake craniotomy forrain tumor from remote antiquity. They provide funda-ental information about the usefulness of awake surgery ine treatment of brain disease. Interestingly, they also give use outline of the development of awake surgery in Asia,specially in Japan, the developed country in Asia.We have a different opinion about awake surgery in China,

oth the history and at present. As neurosurgeons in China, weitness the development of neurosurgery in China; and wenderstand the limitations in the authors' introduction becausee could not provide them enough literature in English.We reviewed the literature in Chinese about awake

raniotomy for brain tumors. We add our opinion to give therticle some supplemental data. As early as 1965, theeurosurgeons in China started to perform awake surgerysing the unique techniques of acupuncture for brain tumors.hey accumulated successful cases and also tried to set upe standards for the technique. In 1979, the Chinese

National Cooperative Group for Acupuncture Anesthesia