awake maping optimize extent of resection - deffau nsurg 2010

8/4/2019 Awake Maping Optimize Extent of Resection - Deffau NSurg 2010

1/11

CLINICAL STUDIES

1074 | VOLUME 66 | NUMBER 6 | JUNE 2010 www.neurosurgery-online.com

Alessandro De Benedictis, MD

Department of Surgical Sciences,

Neurosurgical Unit,

University of Insubria,

Varese, Italy

Sylvie Moritz-Gasser, ST

Department of Neurosurgery,

Hpital Gui de Chauliac,

CHU Montpellier,

Montpellier, France

Hugues Duffau, MD, PhDDepartment of Neurosurgery,

Hpital Gui de Chauliac,

and Institut of Neuroscience of

Montpellier,

INSERM U583,

Plasticity of Central Nervous System,

Human Stem Cells and Glial Tumors,

Hpital Saint Eloi,

CHU Montpellier,

Montpellier, France

Reprint requests:

Hugues Duffau, MD, PhD,

Department of Neurosurgery, Hpital Gui

de Chauliac, CHU Montpellier,

80 Av Augustin Fliche, 34295 Montpellier,France.

E-mail: [email protected]

Received, March 4, 2009.

Accepted, November 30, 2009.

Copyright 2010 by the

Congress of Neurological Surgeons

Recent studies have demonstrated that awakecraniotomy with intraoperative electricalbrain mapping represents a reliable method

to minimize the risk of permanent deficit dur-ing surgery for tumors located within eloquentareas.1-10This method enabled the extent of indi-cations of surgery in regions classically consid-ered inoperable while preserving the quality oflife, especially for infiltrative tumors such as low-

grade glioma.11 However, it could be argued thatpreservation of functional sites might lead to alesser degree of tumor removal. To the best of ourknowledge, the extent of resection was neverdirectly compared between traditional andawake procedures except in 2 previous reports:one by Reithmeier et al12 and one by our team.11

Even though both observed a better extent ofresection with intraoperative mapping, the com-parison was made with a control group and notin the same patients.

Here, we report for the first time a surgicalseries of 9 patients who underwent 2 consecu-tive surgeries for the same tumor in eloquentareas, the first one without and then the secondone with awake mapping. We show the statisti-

cally significant contribution of the awake proce-dure to optimize the extent of resection of low-grade glioma located within eloquent regions.

PATIENTS AND METHODS

Nine right-handed patients (3 male and 6female) ranging in age from 19 to 69 years(median, 39 years), underwent 2 consecutive sur-gical resections of a supratentorial low-grade

ABBREVIATIONS: FLAIR, fluid-attentuated inver-sion recovery; WHO, World Health Organization

Awake Mapping Optimizes the Extent of Resectionfor Low-Grade Gliomas in Eloquent Areas

BACKGROUND: Awake craniotomy with intraoperative electrical mapping is a reliablemethod to minimize the risk of permanent deficit during surgery for low-grade gliomalocated within eloquent areas classically considered inoperable. However, it could beargued that preservation of functional sites might lead to a lesser degree of tumor removal.

To the best of our knowledge, the extent of resection has never been directly comparedbetween traditional and awake procedures.

OBJECTIVE: We report for the first time a series of patients who underwent 2 consecutivesurgeries without and with awake mapping.

METHODS: Nine patients underwent surgery for a low-grade glioma in functional sitesunder general anesthesia in other institutions. The resection was subtotal in 3 cases and

partial in 6 cases. There was a postoperative worsening in 3 cases. We performed a secondsurgery in the awake condition with intraoperative electrostimulation. The resection wasperformed according to functional boundaries at both the cortical and subcortical levels.

RESULTS: Postoperative magnetic resonance imaging showed that the resection was com-plete in 5 cases and subtotal in 4 cases (no partial removal) and that it was improved in allcases compared with the first surgery (P= .04). There was no permanent neurological wors-ening. Three patients improved compared with the presurgical status. All patients returnedto normal professional and social lives.

CONCLUSION: Our results demonstrate that awake surgery, known to preserve the qual-ity of life in patients with low-grade glioma, is also able to significantly improve the extentof resection for lesions located in functional regions.

KEY WORDS: Awake surgery, Direct electrical stimulation, Functional brain mapping, Low-grade glioma

Neurosurgery 66:1074-1084, 2010 DOI: 10.1227/01.NEU.0000369514.74284.78 www.neurosurgery-online.com


2/11

glioma located within eloquent (language and/or sensory-motor)areas. The first operation was performed between 1997 and 2006in 9 other institutions by 9 surgeons specialized in removing braingliomas, even if they did not use intraoperative functional map-ping. The second surgery was systematically performed between2006 and 2008 by the same neurosurgeon (H.D.) using intraop-

erative electrical mapping in awake patients.For the second operation, the same protocol was administrated

to all patients as previously reported.5,11,13Preoperatively, in additionto neurological examination, language was tested by the same speechtherapist (S.M.G.) using the Boston Diagnostic Aphasia Examina-tion.14 Hemispheric dominance was assessed with a standardizedquestionnaire (Edinburgh inventory).15 The topography and thevolume of the tumor recurrence were accurately analyzed on a pre-operative magnetic resonance image (MRI; T1-weighted and spoiled-gradient images obtained before and after gadolinium enhancementin the 3 orthogonal planes, T2-weighted axial coronal images, andfluid-attentuated inversion recovery [FLAIR]weighted axial images).

All patients underwent awake surgery under local anesthesia sothat functional, especially language, cortical, and subcortical map-ping could be carried out with direct electrical stimulation.4,5,11,13,16-23A bipolar electrode with 5-mm-spaced tips delivering a biphasiccurrent (pulse frequency, 60 Hz; single pulse phase duration, 1 ms;amplitude, 2-8 mA) (Nimbus, Hemodia, Labge, France) wasapplied to the brain of awake patients. In the first stage, corticalmapping was performed after tumor and sulci/gyri identificationwith ultrasonography and before resection. Sensory-motor mappingwas performed first, with the goal of obtaining a positive response.Under local anesthesia, the current intensity adapted to each patientwas determined by progressively increasing the amplitude in1-mA increments, from a baseline of 2 mA, until a sensory-motor

response was elicited (ie, an involuntary movement and/or a per-ception of dysesthesia was reproducibly described by the patient),with 8 mA as the upper limit, with the goal of avoiding the gen-eration of seizures. Then, the patient was asked to perform count-ing and picture naming24 (preceded by a short sentence to read,namely the French translation of this is a, to check that therewere no seizures generating complete speech arrest if the patientwas not able to name) to identify the essential cortical languagesites known to be inhibited by stimulation. The patient was neverinformed when the brain was stimulated. The duration of eachstimulation was 4 seconds. At least 1 picture presentation withoutstimulation separated each stimulation, and no site was stimulatedtwice in succession to avoid seizures. Each cortical site (size, 55 mm

because of the spatial resolution of the probe) of the entire cortexexposed by the bone flap was tested 3 times. It is currently accepted,since the seminal publication of Ojemann et al,25 that 3 trials aresufficient to ensure whether a cortical site is essential for language,eg, generating disturbances during its 3 stimulations, with nor-malization of language as soon as the stimulation is stopped. Thetype of language disturbances was detailed by a speech therapist(S.M.G.), who was always present in the operative room duringthe functional mapping, using a classification previously detailed.5,19

Each eloquent area was marked with a sterile number tag on the brain

surface, and its location was correlated to the anatomic landmarks(sulci/gyri/tumor boundaries) previously identified by ultrasonog-raphy. A photograph of the cortical map was systematically madebefore resection. During the second surgical stage, the glioma wasremoved by alternating resection and subcortical stimulations. Thefunctional pathways were followed progressively from the cortical

eloquent sites already mapped to the depth of the resection. Thepatient had to continue to name when the resection became closeto the subcortical crucial structures, which were also identified byfunctional inhibition during stimulation at the cortical level. Again,the type of disturbance was detailed by a speech therapist through-out the resection. To perform the best possible tumor removal withpreservation of the functional areas, all resections were pursueduntil eloquent pathways were encountered around the surgical cav-ity, ie, according to functional boundaries. Thus, there was no mar-gin left around the cortico-subcortical eloquent areas.

Postoperative functional outcome was assessed with the same pro-tocol as before surgery, during the immediate postoperative stage,at 3 months, and then every 6 months after surgery. A controlMRI was performed in all cases immediately, at 3 months, andthen every 6 months after surgery. This imaging enabled us toevaluate the extent of glioma removal, interpreted by 2 observers(A.D.B. and H.D.) according to the classification method reportedby Berger et al26: total resection if no residual signal abnormalityon FLAIR-weighted MRI, subtotal resection if 10 mL residue. Postoperative tumor vol-ume evaluated on the MRI 3 months after the first surgery wascompared with the postoperative tumor volume evaluated on theMRI 3 months after the second surgery with a Fisher exact test(a significance level of 5% [P< .05] was accepted).

RESULTSClinical, radiological, and surgical results for the 9 patients before

and after both surgeries are summarized in Tables 1 through 3.

First Surgery

The presenting symptoms were seizures in all patients (3 gen-eralized, 6 partial). The preoperative neurological evaluationshowed mild memory disturbances in only 1 patient (Table 1).

The preoperative MRI demonstrated in all patients a T1-weightedhypointense and T2-weighted hyperintense lesion without enhance-ment after gadolinium injection (Figures 1A and 2A). In 8 patients,the tumor was located in the left dominant hemisphere: 5 within

the left frontal region, 1 within the left superior temporal gyrus, and2 within the left parietal lobe. In 1 patient, the lesion was locatedin the right parietooccipital junction, with an anterior tumoralinvolvement coming very close to the primary somatosensory area.The 9 patients underwent surgery under general anesthesia in otherinstitutions.

No permanent postsurgical neurological worsening was inducedat standard examination except 2 mild dysphasias. However, noextensive functional assessment was performed after the first sur-gery, especially concerning language. Postoperative MRI revealed

NEUROSURGERY VOLUME 66 | NUMBER 6 | JUNE 2010 | 1075

AWAKE SURGERY AND EXTENT OF RESECTION


3/11


DE BENEDICTIS ET AL

FIGURE 1. A, axial fluid-attentuated inversionrecovery (FLAIR)weighted (left), sagittal (mid-dle), and coronal (right) enhanced T1-weightedmagnetic resonance imagining (MRI) showing alow-grade glioma involving the left inferior frontalgyrus. B, axial FLAIR-weighted (left), axial (mid-dle,) and coronal (right) enhanced T1-weightedMRI after surgery performed under general anes-thesia showing a partial resection of the lesion (20%

of preoperative volume, ie, 84 cm3

).C

, axial T2-weighted (left), sagittal (middle,) and coronal (right)enhanced T1-weighted MRI showing the residualtumor before the second surgery, with a growth esti-mated from 83 to 89 cm3 in 6 months. D, intraop-erative photographs before (left) and after (right)resection of the lesion performed under local anes-thesia. The letters correspond to the limits of thetumor identified with intraoperative ultrasonogra-phy. The eloquent cortical sites were marked bynumbers as follows: 25, 27, and 26, ventral pre-motor cortex inducing articulatory disturbances;and 23 and 24, dorsal premotor cortex inducingsemantic paraphasias when stimulated. The leftinferior frontal gyrus was removed because no func-

tional troubles were elicited by stimulation in thisregion. The resection was extended deeply until thearcuate fasciculus, where the stimulation evokedphonemic paraphasias (50); the head of the cau-date nucleus superiorly, generating perseverationswhen stimulated (49); and the descending fibersfrom the ventral premotor cortex, where stimula-tion generated articulatory disturbances (45). E,Postoperative axial T2-weighted (left), sagittal (mid-dle), and coronal (right) enhanced T1-weightedMRI showing an almost total tumor resection (4cm3 residue). The patient returned to a normalsocioprofessional life, with an improvement in qual-ity of life compared with the preoperative status.

B

A

C

D

E


4/11



no complete resections, 3 subtotal resections (residue 10 cm3 residue) (Figures 1B, 2B, 3Aand 4A). The mean volume of residual tumor was 29 cm3 (range,6-84 cm3). Histological examination revealed a World Health

Organization (WHO) grade II glioma in 8 patients and a WHOgrade I glioma in 1 patient (ganglioglioma). Three patients didnot return to their professional activity after the operation becauseof a mild dysphasia in 2 and a depressive syndrome in 1. Duringfollow-up, 4 patients received chemotherapy (temozolomide) asadjuvant treatment, which was combined with radiotherapy in 1patient.

Second Surgery

When referred to our department, 7 patients presented withseizures (6 partial, 1 generalized), which were medically intractablein 3 patients. One patient also had an anxious-depressive syn-drome. One patient was without any symptoms (Table 2).

The preoperative clinical evaluation and Boston DiagnosticAphasia Examination revealed neurological disturbances in 7patients: speech, memory, writing, and concentration disordersin 4 patients with a left frontal glioma tumor and in the patientwith a left temporal tumor; a quadrantanopsia for the patient har-boring the right occipitoparietal lesion; and a right somatosen-sory deficit with ataxia for the patient with a left parietal tumor.Two patients had a normal examination.

In the 9 patients, the preoperative MRI showed a volumetricincrease in the residual glioma compared with the MRI performed

after the first surgery (Figures 1C, 2C, 3B and 4B). The meantumor volume was 45 cm3 (range, 13-90 cm3). In 3 patients (1with right parietooccipital and 2 with left frontal lesions), anenhancement was visible after gadolinium injection.

The mean delay between the first and second surgeries was 57months (range, 8-120 months).

The 9 surgeries were performed under local anesthesia (Figures1D, 2D, 3C and 4C). All patients tolerated the awake phase ofthe surgery well. Eloquent sites were identified in all patientsthrough the use of intraoperative electrical stimulation with nonegative mapping. The resection was pursued until both corti-cal and subcortical functional structures were encountered to opti-mize the extent of tumor removal. The median time of surgerywas 4 hours.

The clinical evaluation in the immediate postoperative periodnoted a transient worsening in language performance in 4 patients.The patient with the right parietooccipital tumor presented tran-

sitory finger dysesthesia. Moreover, in 1 patient, a mild deficit ofaccurate movements of the left fingers was observed over 5 days.Three patients had a normal examination immediately followingthe second operation.

The median length of hospital stay was 1 week, and 5 patientsunderwent language rehabilitation at home. All patients improvedtheir neurological status relative to their immediate postoperativecondition within weeks after surgery; they recovered to their pre-operative condition, particularly overcoming speech disturbances.The 2 patients who interrupted their professional activity because

a WHO, World Health Organization; RT, radiotherapy; CT, chemotherapy.

TABLE 1. Clinical, Radiological, and Pathological Characteristics Concerning the First Surgerya

Patient/

Sex/Age, y

Presenting

Symptoms

Clinical

ExaminationLocation Year

Extent of

ResectionPathology (WHO)

Adjuvant

Therapy

1/F/19 Partial seizures Memory

disturbances

Left superior

temporal gyrus

2006 Subtotal Ganglioglioma no

2/M/48 Partial seizures Normal Right parieto-

occipital

1999 Partial WHO II glioma RT/CT (temozo-

lomide)

3/F/41 Partial seizures

with speech

Normal Left inferior

frontal gyrus

2006 Partial WHO II glioma No

4/F/21 Partial seizures Normal Left premotor

frontal

2002 Subtotal WHO II glioma No

5/M/69 Partial seizures Normal Left frontal 2000 Partial WHO II glioma CT (temozo-

lomide)

6/F/43 Generalized

seizures

Normal Left frontal 2006 Partial WHO II glioma CT (temozo-

lomide)

7/F/39 Generalized

seizures

Normal Left parietal 2005 Partial WHO II glioma CT (temozo-

lomide)

8/M/39 Generalized

seizures

Normal Left frontal 2003 Subtotal WHO II glioma No

9/F/35 Partial seizures Normal Left Retro-

central gyrus

1997 Partial WHO II glioma No


5/11


DE BENEDICTIS ET AL

FIGURE 2. A, axial T2-weighted (left), coronal(middle), and sagittal (right) T1-weighted mag-netic resonance imaging (MRI) before the first sur-gery performed under general anesthesia showing aleft frontal low-grade glioma. B, postoperative axial fluid-attentuated inversion recovery (FLAIR)weighted (left, middle) and coronal T1-weightedMRI (right) control, showing a partial resection ofthe tumor. C, axial (left), coronal (middle), and

sagittal (right) enhanced T1-weighted MRI 8 yearsafter the first surgery showing the volumetric increasein lesion residue (from 12-25 cm3) with the occur-rence of an enhancement. D, Photographs showingintraoperative view before (left) and after (right)the resection performed under local anesthesia. Theletters correspond to the limits of the tumor identi-fied using intraoperative ultrasonography. Corticalmapping allowed identification of the eloquent sitesas follows: 1, ventral premotor cortex elicitinganarthria during stimulation; 5 and 3, pars oper-cularis of left inferior frontal gyrus inducing phone-mic paraphasias when stimulated; and 4, semanticparaphasia elicited by stimulation of the dorsolat-eral prefrontal cortex. The resection was performed

according to functional boundaries, with identifi-cation of the subcortical pathways as follows: 43,anterior part of the inferior fronto-occipital fascicu-lus inducing semantic paraphasias when stimulated;45, descending fibers from the ventral premotor cor-tex inducing articulatory disturbances when stim-ulated; and 50, superior fibers of the inferiorfronto-occipital fasciculus coming in contact withthe dorsolateral prefrontal cortex and eliciting seman-tic paraphasias during stimulation. E, postopera-tive axial (left), coronal (middle), and sagittal (right)enhanced T1-weighted MRI demonstrating com-plete resection of the tumor. The patient returnedto a normal socioprofessional life with no deficit.

B

A

C

D

E


6/11



of language disorders after the first surgery returned to work. Thepatient who experienced a depressive syndrome after the first oper-ation returned to a normal social life, finished her studies, andstarted to work. Thus, there was no morbidity resulting from thesecond surgery. The quality of life improved in these 3 patientsrelative to their preoperative condition.

Pathological examinations confirmed a WHO grade I glioma(ganglioglioma) in 1 patient and a WHO grade II glioma in 5patients. In the 3 patients with a contrast enhancement on thepreoperative MRI, anaplastic foci were identified.

Postoperative MRI showed complete resection in 4 patients,subtotal removal in 5 patients (


7/11


DE BENEDICTIS ET AL

recent years (522 operations in the last 5 years instead of 358 oper-ations in the previous 9 years). In the present study, we confirmthe improvement in functional results owing to intraoperativeawake mapping, especially concerning language performance,seizure control, and thus optimization of socioprofessional qual-ity of life. After the first surgery performed under general anes-

thesia, 3 patients did not return to their professional activity, in 2cases because of mild dysphasia. After the second operation, per-formed under awake conditions and with postsurgical speech ther-apy, all patients returned to work.

However, neurosurgeons have to keep in mind that the firstgoal of surgery for low-grade glioma is to maximize the extent of

FIGURE 3. A, axial fluid-attentuatedinversion recovery (FLAIR)weighted(left), coronal T2-weighted (middle),and sagittal enhanced T1-weighted

(right) magnetic resonance imagine(MRI) showing partial resection of aleft parietal low-grade glioma after sur-gery performed under general anesthe-sia. B, axial FLAIR-weighted (left),coronal enhanced T1-weighted (middle,)and sagittal T2-weighted MRI (right)showing the lesion growth after 3 years,with a volumetric increase from 65 to90 cm3. C, intraoperative photographsduring a second surgery performed underlocal anesthesia showing the corticallandmarks. Intraoperative photographsbefore (left) and after (right) resectionof the lesion performed under local anes-thesia. The letters correspond to the lim-its of the tumor identified with intra-operative ultrasonography. The eloquentcortical sites were marked by numbersas followed: 47, left ventral premotorcortex inducing anarthria during stim-ulation; 2, primary motor cortex of theface; 50, primary motor cortex of thehand; within the retrocentral gyrus,primary somatosensory cortex of the face(4), fingers (48, 6, 5, 7), and forearm(8). The resection was performed accord-ing to functional boundaries, with iden-tification, at the level of the subcortical

white matter, of the somatosensory thal-amocortical fibers inducing dysesthe-sias in the upper (39) and lower (46)limb, and of the arcuate fasciculus (38),eliciting phonemic paraphasias duringstimulation. D, immediate postopera-tive FLAIR axial (left), coronal (mid-dle), and sagittal (right) enhanced T1-weighted MRI showing a subtotalglioma removal with a residue (3 cm3)in the anterior part of the surgical cav-ity, where somatosensory fibers repre-sented the anterior limit of resection.The patient returned to a normal socio-professional life with no deficit.

B

A

C

D


8/11

lead to a smaller degree of resection. To the best of our knowl-edge, the extent of glioma removal was never directly comparedbetween traditional and awake procedures, except in 2 previous stud-ies by Reithmeier et al12 and by our team.11 Nonetheless, eventhough both reported an improved extent of resection with intra-operative mapping, the comparison was made with a control group

and not in the same patients.The present study is, to the best of our knowledge, the first

that evaluates the 2 surgical modalities in the same patients. As aconsequence, the fact that both surgeries were performed consec-utively for low-grade gliomas located in the same eloquent regionsenabled us to objectively compare the extent of resection withoutand then with the use of awake mapping.

In the first surgery, performed under general anesthesia, thechoice of surgical limits resulted from the macroscopic evidenceof the visible pathological tissue. However, it is well known thatlow-grade glioma is an invasive, poorly circumscribed lesion. Asa consequence, on the basis of purely anatomic criterion, whenthe tumor is located in presumably eloquent areas, the extent ofresection is decreased to avoid permanent deficit. In the pres-ent study, there was no complete resection, only 3 subtotal resec-tions and 6 partial resections, with a high mean volume of residue29 cm3. In addition, despite these precautions, 2 patients hada moderate but objective language worsening, preventing themfrom working.

On the contrary, during second surgery, direct cerebral stimu-lation enabled the surgeon to define a map specific for each patientand to take into account the interindividual anatomofunctionalvariability to tailor the resection according to functional bound-aries at both the cortical and subcortical levels.5,21As a conse-quence, the glioma removal was pursued until eloquent structures

were encountered, not before.11

Interestingly, this methodologyallowed us to take a margin around the tumor, eg, in patients 2 and4. Such strategy based on intrasurgical awake mapping enabledthe maximization of the extent of glioma resection beyond thevisible limits of the tumor-because it is now known that tumorcells invade brain tissue far away from the boundaries of the tumorimage-but without inducing permanent deficit. Even withincrucial areas, thanks to mechanisms of brain plasticity exten-sively described in cases of slow-growing lesions such as low-gradegliomas,18,20,41 intraoperative awake mapping allows opening thedoor to an increased extent of resection than that based on purelyanatomic criterion. In the present study, there was no partial resec-tion after the second surgery, with a mean volume of residual

tumor of only 1.6 cm3, significantly reduced compared with themean residue left after the first operation. These results can beexplained by the fact that it was possible to remove parts of tumorlocated in regions classically considered crucial for function becauseof functional reshaping shown by intraoperative mapping but thatthese portions of glioma were judged a priori as inaccessible dur-ing the first intervention. Interestingly, despite optimization oflesion removal because no margin was left around the eloquentstructures detected by electrostimulation,5 it is worth noting thatthe brain function and quality of life of patients were preserved and



resection. Despite the lack of phase III studies, there is growing evi-dence that more extensive tumor removal may be associated witha more favorable life expectancy for patients with low-grade gliomasby delaying the anaplastic transformation.10,18,28,51-58Therefore,it could be argued that the use of intraoperative mapping withpreservation of eloquent cortical and subcortical structures might

TABLE 3. Comparison of Residual Volume of Glioma After the

First and Second Surgeriesa

First Surgery Second Surgery

Postop- Extent Preop- Postop- Extent

erative of erative erative of

Follow-Patient

Volume, Resec- Volume, Volume, Resec-

up, mo

cm3 tion cm3 cm3 tion

1 12 ST 12 0 T 27

2 41 P 43 2 ST 27

3 84 P 89 4 ST 20

4 6 ST 25 5 ST 13

5 13 P 25 0 T 8

6 10 P 13 0 T 8

7 65 P 90 3 ST 7

8 8 ST 65 0 T 4

9 20 P 0 T 3

a ST, subtotal; T, total; P, partial.

TABLE 4. Permanent Neurological Deficit Reported in the

Literature From 2003 After Surgery of Gliomas Performed With

Intraoperative Electrical Mappinga

Severe PermanentGliomas (WHO II

PostoperativeAuthors (Year) Gliomas When

Deficits, nAvailable), n

patients (%)

Keles et al (2004)32 294 14 (4.8)

Otani et al (2005)7 21 (9) 0

Bello et al (2006)2 7 0

Benzagmout et al (2007)41 7 (7) 0

Bello et al (2007)2 88 (44) 2 (2.3)

Sakurada et al (2007)49 3 (2) 0

Carrabba et al (2007)43 146 14 (10)

Low et al (2007)46 13 (7) 1

Serletis et al (2007)10 367 (137) 13

Sanai et al (2008)8 250 (124) 8 (3.2)

Ilmberger et al (2008)6 142 (74) 6 (3.9)

Amorim (2008)45 7 (3) 1 (14.2)

Duffau et al (2008)5 115 (115) 2 (1.7)

Total 1460 (522) 61 (4.1)

a WHO, World Health Organization.


9/11


DE BENEDICTIS ET AL

even improved compared with the first surgery because all patientsare now working.

However, we have to acknowledge 3 limitations of our studies.First, there was a significant time interval between surgeries.Interestingly, taking into account this significant time intervalbetween surgeries and the fact that all WHO grade II gliomas aregrowing tumors, the mean volume of the lesion before the sec-ond surgery was greater than the mean volume after the first resec-tion (Table 3). Consequently, it was not obvious that the amountof resection could be greater in the second surgery, especially

because of the location of the gliomas within eloquent areas.Second, in the statistical comparison of residual tumor volumes withand without mapping, there is a bias resulting from poor resec-tion in some first procedures, which had been performed in anotherinstitution and which could have been much more extended evenwithout mapping, particularly the portions of those tumors thatwere not directly adjacent to eloquent areas. Third, the reliabil-ity of electrical mapping should be discussed. We have alreadyreported that the reliability of the initial cortical mapping wasconfirmed by the subcortical mapping, and the congruence between

FIGURE 4. A, Axial fluid-attentuatedinversion recovery (FLAIR)weighted(left), sagittal T1-weighted (middle),and coronal T2-weighted (right) mag-netic resonance imagine (MRI) show-ing a partial resection of a right parieto-occipital low-grade glioma after a surgeryperformed under general anesthesia. B,axial (left), sagittal (middle), and coro-nal (right) enhanced T1-weighted MRIshowing the growth of the residualtumor, with a very slow volumetricincrease (from 41 to 43 cm3 in 84months, after radiotherapy and chemo-therapy) but with the occurrence of anenhancement in the posterior part. C,intraoperative photographs before (left)

and after (right) resection of the lesionperformed under local anesthesia. Theletters correspond to the limits of thetumor identified with intraoperativeultrasonography. The eloquent corticalsites were marked by numbers as fol-lowed: 1, primary motor cortex of thehand; 5, primary somatosensory cortexof the forearm; and 2, 4, 9, and 5, pri-mary somatosensory cortex of the fin-gers. The resection was performed accord-ing to functional boundaries, withidentification, at the level of the sub-cortical white matter and of thesomatosensory thalamocortical fibers

inducing dysesthesias in the upper (10)and lower (11) limb when stimulated.D, postoperative FLAIR-weighted axial(left), sagittal (middle), and coronal(right) T1-weighted MRI showing asubtotal glioma removal (2 cm3 ofresidue in the depth). The patientreturned to a normal socioprofessionallife with no deficit.

B

A

C

D


10/11

these maps (gray and white matter) guarantees the practitionerthat the organization of the network (and not only isolated cor-tical epicenters) has been correctly understood.5 Furthermore, thepatient continued to perform tasks throughout the resection,allowing the surgeons to check the anatomofunctional integrity ofthe eloquent circuits online, in addition to the data provided by

the electrical mapping. However, we acknowledge that there isstill a risk of false positives with electrostimulation. We have nev-ertheless demonstrated that awake mapping allows an increase inthe extent of resection while preserving brain function despite thefact that the specificity of cortico-subcortical electrical mappingremains a matter of concern.

CONCLUSION

We show not only that the use of intraoperative direct awake brainstimulation during surgery of low-grade gliomas enables the sur-geon to perform a resection according to functional boundaries,minimizing postoperative morbidity and even improving qualityof life, but also that this technique has a quantitative impact onthe extent of resection. The direct comparison between the resultsobtained after consecutive surgeries without and then with elec-trical mapping in the same patient demonstrates for the first timeand for sequential surgeries better resection with mapping thanwith traditional surgery under general anesthesia.

The paucity of cases discussed in this study in relation to theperiod considered and the average number of cases of low-gradegliomas treated by the same senior author (250) suggests that agrowing number of patients underwent surgery with the help ofawake brain mapping because this technique is increasingly safe,achievable, and reproducible. Therefore, the continuation of its

spread is desirable, thanks to multidisciplinary and multicenterstudies, with a greater standardization of criteria for data collec-tion, which is essential for a more objective comparison of resultsbetween different managements.

Disclosure

The authors have no personal financial or institutional interest in any of thedrugs, materials, or devices described in this article.

REFERENCES

1. Bello L, Acerbi F, Giussani C, et al. Intraoperative language localization in multi-lingual patients with gliomas. Neurosurgery. 2006;59(1):115-125.

2. Bello L, Gallucci M, Fava M, et al. Intraoperative subcortical language tract map-

ping guides surgical removal of gliomas involving speech areas. Neurosurgery.2007;60(1):67-82.

3. Chang EF, Potts MB, Keles GE, et al. Seizure characteristics and control followingresection in 332 patients with low-grade gliomas.J Neurosurg. 2008;108(2):227-235.

4. Duffau H. Intraoperative cortico-subcortical stimulations in surgery of low-gradegliomas. Expert Rev Neurother. 2005;5(4):473-485.

5. Duffau H, Peggy Gatignol ST, Mandonnet M, Capelle L, Taillandier L. Intraoperativesubcortical stimulation mapping of language pathways in a consecutive series of115 patients with grade II glioma in the left dominant hemisphere.J Neurosurg.2008;109(3):461-471.

6. Ilmberger J, Ruge M, Kreth FW, Briegel J, Reulen HJ, Tonn JC. Intraoperativemapping of language functions: a longitudinal neurolinguistic analysis.J Neurosurg.2008;109(3):583-592.

7. Otani N, Bjeljac M, Muroi C, et al. Awake surgery for glioma resection in eloquentareas: Zurichs experience and review. Neurol Med Chir (Tokyo). 2005;45(10):501-511.

8. Sanai N, Mirzadeh Z, Berger MS. Functional outcome after language mapping forglioma resection. N Engl J Med. 2008;358(1):18-27.

9. Sanai N, Berger MS. Glioma extent of resection and its impact on patient out-come. Neurosurgery. 2008;62(4):753-766.

10. Serletis D, Bernstein M. Prospective study of awake craniotomy used routinely

and nonselectively for supratentorial tumors.J Neurosurg. 2007;107(1):1-6.11. Duffau H, Lopes M, Arthuis F, et al. Contribution of intraoperative electrical stim-ulations in surgery of low grade gliomas: a comparative study between two serieswithout (1985-96) and with (1996-2003) functional mapping in the same insti-tution.J Neurol Neurosurg Psychiatry. 2005;76(6):845-851.

12. Reithmeier T, Krammer M, Gumprecht H, Gerstner W, Lumenta CB. Neuro-navigation combined with electrophysiological monitoring for surgery of lesions ineloquent brain areas in 42 cases: a retrospective comparison of the neurologicaloutcome and the quality of resection with a control group with similar lesions.Minim Invasive Neurosurg. 2003;46(2):65-71.

13. Duffau H, Capelle L, Denvil D, et al. Usefulness of intraoperative electrical sub-cortical mapping during surgery for low-grade gliomas located within eloquentbrain regions: functional results in a consecutive series of 103 patients.J Neurosurg2003;98(4):764-778.

14. Goodglass H, Kaplan E.The Assessment of Aphasia and Related Disorders. Philadelphia,Pa: Lea and Fibiger; 1972.

15. Olfield RC. The assessment and analysis of handedness: the Edinburgh inventory.Neuropsychologia. 1971;9(1):97-113.16. Duffau H, Capelle L, Sichez N, et al. Intraoperative mapping of the subcortical

language pathways using direct stimulations: an anatomo-functional study. Brain.2002;125(pt 1):199-214.

17. Duffau H, Capelle L, Denvil D, et al. The role of dominant premotor cortex inlanguage: a study using intraoperative functional mapping in awake patients.Neuroimage. 2003;20(4):1903-1914.

18. Duffau H. Lessons from brain mapping in surgery for low-grade glioma: insightsinto associations between tumour and brain plasticity. Lancet Neurol. 2005;4(8):476-486.

19. Duffau H, Gatignol P, Mandonnet E, Peruzzi P, Tzourio-Mazoyer N, Capelle L.New insights into the anatomo-functional connectivity of the semantic system: astudy using cortico-subcortical electrostimulations. Brain. 2005;128(pt 4):797-810.

20. Duffau H. New concepts in surgery of WHO grade II gliomas: functional brain map-ping, connectionism and plasticity: a review.J Neurooncol. 2006;79(1):77-115.

21. Duffau H. Contribution of cortical and subcortical electrostimulation in brainglioma surgery: methodological and functional considerations. Neurophysiol Clin.2007;37(6):373-382.

22. Duffau H. The anatomo-functional connectivity of language revisited: new insightsprovided by electrostimulation and tractography. Neuropsychologia. 2008;46(4):927-934.

23. Duffau H. Intraoperative neurophysiology during surgery for cerebral tumors. In:Nuwer MR, ed. Handbook of Clinical Neurophysiology: Intraoperative Monitoringof Neural Function. Boston, Mass: Elsevier; 2008;8:491-507

24. Metz-Lutz MN, Kremin H, Deloche G, et al. Standardisation dun test de dnom-ination orale: contrle des effets de lge, du sexe et du niveau de scolarit chez lessujets adultes normaux. Rev Neuropsychol. 1991;1(1):73-95.

25. Ojemann G, Ojemann J, Lettich E, Berger M. Cortical language localization inleft, dominant hemisphere: an electrical stimulation mapping investigation in 117patients.J Neurosurg. 1989;71(3):316-326.

26. Berger MS, Deliganis AV, Dobbins J, Keles GE. The effect of extent of resection

on recurrence in patients with low grade cerebral hemisphere gliomas. Cancer.1994;74(6):1784-1791.27. Abeloos L, Brotchi J, De Witte O. Management of low-grade glioma: a retrospec-

tive study concerning 201 patients [in French]. Neurochirurgie. 2007;53(4):277-283.

28. Berger MS. Lesions in functional (eloquent) cortex and subcortical white mat-ter. Clin Neurosurg. 1994;41:444-463.

29. Brown PD. Low-grade gliomas: the debate continues. Curr Oncol Rep. 2006;8(1):71-77.

30. Duran I, Raizer JJ. Low-grade gliomas: management issues. Expert Rev AnticancerTher. 2007;7(suppl 12):S15S21.

31. Gilbert MR, Lang FF. Management of patients with low-grade gliomas. NeurolClin. 2007;25(4):1073-1088.




11/11


DE BENEDICTIS ET AL

32. Keles GE, Lundin DA, Lamborn KR, Chang EF, Ojemann G, Berger MS.Intraoperative subcortical stimulation mapping for hemispherical perirolandicgliomas located within or adjacent to the descending motor pathways: evaluationof morbidity and assessment of functional outcome in 294 patients.J Neurosurg.2004;100(3):369-375.

33. Lang FF, Gilbert MR. Diffusely infiltrative low-grade gliomas in adults.J ClinOncol. 2006;24(8):1236-1245.

34. Laws ER, Shaffrey ME, Morris A, Anderson FA Jr. Surgical management of intracra-nial gliomas: does radical resection improve outcome?Acta Neurochir Suppl.2003;85:47-53.

35. Mandonnet E, Pallud J, Clatz O, et al. Computational modeling of the WHOgrade II glioma dynamics: principles and applications to management paradigm.Neurosurg Rev2008;31(3):263-269.

36. Mandonnet E, Jbabdi S, Taillandier L, et al. Preoperative estimation of residualvolume for WHO grade II glioma resected with intraoperative functional map-ping. Neuro Oncol. 2007;9(1):63-69.

37. Pouratian N, Asthagiri A, Jagannathan J, Shaffrey ME, Schiff D. Surgery insight:the role of surgery in the management of low-grade gliomas. Nat Clin Pract Neurol.2007;3(11):628-639.

38. Pouratian N, Mut M, Jagannathan J, Lopes MB, Shaffrey ME, Schiff D. Low-grade gliomas in older patients: a retrospective analysis of prognostic factors. JNeurooncol. 2008;90(3):341-350.

39. Schmidt MH, Berger MS, Lamborn KR, et al. Repeated operations for infiltrativelow-grade gliomas without intervening therapy.J Neurosurg. 2003;98(6):1165-1169.

40. Schramm J, Blmcke I, Ostertag CB, Schlegel U, Simon M, Lutterbach J. Low-gradegliomas: current concepts.Zentralbl Neurochir. 2006;67(2):55-66.

41. Benzagmout M, Gatignol P, Duffau H. Resection of World Health Organizationgrade II gliomas involving Brocas area: methodological and functional considera-tions. Neurosurgery. 2007;61(4):741-753.

42. Berger MS. Minimalism through intraoperative functional mapping.Clin Neurosurg.1996;43:324-337.

43. Carrabba G, Fava E, Giussani C, et al. Cortical and subcortical motor mapping inrolandic and perirolandic glioma surgery: impact on postoperative morbidity andextent of resection.J Neurosurg Sci. 2007;51(2):45-51.

44. Carrabba G, Venkatraghavan L, Bernstein M. Day surgery awake craniotomy forremoving brain tumours: technical note describing a simple protocol. MinimInvasive Neurosurg. 2008;51(4):208-210.

45. Amorim RL, Almeida AN, Aguiar PH, et al. Cortical stimulation of language fieldsunder local anesthesia: optimizing removal of brain lesions adjacent to speech areas.

Arq Neuropsiquiatr. 2008;66(3A):534-538.46. Low D, Ng I, Ng WH. Awake craniotomy under local anaesthesia and monitored

conscious sedation for resection of brain tumours in eloquent cortex: outcomes in20 patients.Ann Acad Med Singapore. 2007;36(5):326-331.

47. Picht T, Kombos T, Gramm HJ, Brock M, Suess O. Multimodal protocol forawake craniotomy in language cortex tumour surgery. Acta Neurochir (Wien).2006;148(2):127-138.

48. Pouratian N, Cannestra AF, Bookheimer SY, Martin NA, Toga AW. Variability ofintraoperative electrocortical stimulation mapping parameters across and withinindividuals. J Neurosurg. 2004;101(3):458-466.

49. Sakurada K, Sato S, Sonoda Y, Kokubo Y, Saito S, Kayama T. Surgical resection oftumors located in subcortex of language area.Acta Neurochir (Wien).2007;149(2):123-130.

50. Skirboll SS, Ojemann GA, Berger MS, Lettich E, Winn HR. Functional cortexand subcortical white matter located within gliomas. Neurosurgery. 1996;38(4):678-685.

51. Berger MS, Rostomily RC. Low grade gliomas: functional mapping resection strate-gies, extent of resection, and outcome.J Neurooncol. 1997;34(1):85-101.

52. Chang EF, Smith JS, Chang SM, et al. Preoperative prognostic classification systemfor hemispheric low-grade gliomas in adults.J Neurosurg. 2008;109(5):817-824.

53. Claus EB, Black PM. Survival rates and patterns of care for patients diagnosedwith supratentorial low-grade gliomas: data from the SEER program, 1973-2001.Cancer. 2006;106(6):1358-1363.

54. McGirt MJ, Chaichana KL, Attenello FJ, et al. Extent of surgical resection is inde-pendently associated with survival in patients with hemispheric infiltrating low-

grade gliomas. Neurosurgery. 2008;63(4):700-708.55. Schiff D, Brown PD, Giannini C. Outcome in adult low-grade glioma: the impactof prognostic factors and treatment. Neurology. 2007;69(13):1366-1373.

56. Shaw EG, Berkey B, Coons SW, et al. Recurrence following neurosurgeon-determined gross-total resection of adult supratentorial low-grade glioma: resultsof a prospective clinical trial.J Neurosurg. 2008;109(5):835-841.

57. Smith JS, Chang EF, Lamborn KR, et al. Role of extent of resection in the long-term outcome of low-grade hemispheric gliomas.J Clin Oncol. 2008;26(8):1338-1345.

58. Yeh SA, Ho JT, Lui CC, Huang YJ, Hsiung CY, Huang EY. Treatment outcomesand prognostic factors in patients with supratentorial low-grade gliomas. Br JRadiol. 2005;78(927):230-235.

Acknowledgment

The authors would like to thank Nicolas Menjot de Champfleur, MD, for hishelp with the figures.

COMMENTS

This article illustrates well how the use of awake mapping of the braincan optimize the extent and safety of resection of low-grade gliomas.

The main concern about the study is that the authors demonstration isbased on the comparison with what they consider traditional resection.However, in the 4 provided figures of the postoperative images after ini-tial surgery, the stigmas are those of open biopsies rather traditional (evenpartial) resections. The quality of the results achieved with the use ofawake mapping in their 9 patients constitutes a sufficient argumentationto illustrate the usefulness of the method.

From an oncological point of view, it has been reported that the prog-nosis of the low-grade gliomas depends significantly on the extent of the

removal. This is, of course, especially true for astrocytomas. As far as oligo-dendrogliomas are concerned, one should be circumspect in the appraisalof the oncological value of extremely large resections. It has been wellestablished by pathologists that tumor cells invade brain tissue far awayfrom the boundaries of the tumor, especially through the intrahemi-spheric and even the interhemispheric fascicles and commissures.

In addition, one must not underestimate the limitation and especiallythe pitfalls of brain cortical stimulation, not only because of false-posi-tive but also because of false-negative responses, the latter caused byrefractory phases after stimulation. Plus, white-matter mapping is notvery reliable and has not been codified yet.

The authors should be acknowledged for their intensive work andenergy in promoting awake mapping within the neurosurgical community.

Marc SindouLyon, France

awake maping optimize extent of resection - deffau nsurg 2010

Documents