Awake craniotomy for supratentorial tumors or epileptogenic lesions in pediatric patients: a 16-year retrospective cohort study

Hope M. Reecher Departments of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin

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Jennifer I. Koop Departments of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin

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Ahmed J. Awad Departments of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin

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Irene Kim Departments of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin

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Andrew B. Foy Departments of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin

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Bruce A. Kaufman Departments of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin

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Nicholas A. Meier Departments of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin

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Sean M. Lew Departments of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin

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OBJECTIVE

Awake craniotomy with intraoperative mapping is the widely accepted procedure for adult patients undergoing supratentorial tumor or epileptogenic focus resection near eloquent cortex. In children, awake craniotomies are notably less common due to concerns for compliance and emotional or psychological repercussions. Despite this, successfully tolerated awake craniotomies have been reported in patients as young as 8 years of age, with success rates comparable to those of adults. The authors sought to describe their experience with pediatric awake craniotomies, including insight regarding feasibility and outcomes.

METHODS

A retrospective review was completed for all pediatric (age < 18 years) patients at Children’s Wisconsin for whom an awake craniotomy was attempted from January 2004 until March 2020. Institutional review board approval was granted.

RESULTS

Candidate patients had intact verbal ability, cognitive profile, and no considerable anxiety concerns during neuropsychology assessment. Nine patients presented with seizure. Five patients were diagnosed with tumor and secondary epilepsy, 3 with tumor only, and 3 with epilepsy only. All patients who underwent preoperative functional MRI successfully completed and tolerated testing paradigms. A total of 12 awake craniotomies were attempted in 11 patients, with 1 procedure aborted due to intraoperative bleeding. One patient had a repeat procedure. The mean patient age was 15.5 years (range 11.5–17.9 years). All patients returned to or maintained baseline motor and speech functions by the latest follow-up (range 14–130 months). Temporary deficits included transient speech errors, mild decline in visuospatial reasoning, leg numbness, and expected hemiparesis. Of the 8 patients with a diagnosis of epilepsy prior to surgery, 7 patients achieved Engel class I designation at the 1-year follow-up, 6 of whom remained in class I at the latest follow-up.

CONCLUSIONS

This study analyzes one of the largest cohorts of pediatric patients who underwent awake craniotomy for maximal safe resection of tumor or epileptogenic lesions. For candidate patients, awake craniotomy is safe, feasible, and effective in carefully selected children.

ABBREVIATIONS

fMRI = functional MRI; GTR = gross-total resection; KPS = Karnofsky Performance Scale; STR = subtotal resection; WIS = Wechsler Intelligence Scales.

OBJECTIVE

Awake craniotomy with intraoperative mapping is the widely accepted procedure for adult patients undergoing supratentorial tumor or epileptogenic focus resection near eloquent cortex. In children, awake craniotomies are notably less common due to concerns for compliance and emotional or psychological repercussions. Despite this, successfully tolerated awake craniotomies have been reported in patients as young as 8 years of age, with success rates comparable to those of adults. The authors sought to describe their experience with pediatric awake craniotomies, including insight regarding feasibility and outcomes.

METHODS

A retrospective review was completed for all pediatric (age < 18 years) patients at Children’s Wisconsin for whom an awake craniotomy was attempted from January 2004 until March 2020. Institutional review board approval was granted.

RESULTS

Candidate patients had intact verbal ability, cognitive profile, and no considerable anxiety concerns during neuropsychology assessment. Nine patients presented with seizure. Five patients were diagnosed with tumor and secondary epilepsy, 3 with tumor only, and 3 with epilepsy only. All patients who underwent preoperative functional MRI successfully completed and tolerated testing paradigms. A total of 12 awake craniotomies were attempted in 11 patients, with 1 procedure aborted due to intraoperative bleeding. One patient had a repeat procedure. The mean patient age was 15.5 years (range 11.5–17.9 years). All patients returned to or maintained baseline motor and speech functions by the latest follow-up (range 14–130 months). Temporary deficits included transient speech errors, mild decline in visuospatial reasoning, leg numbness, and expected hemiparesis. Of the 8 patients with a diagnosis of epilepsy prior to surgery, 7 patients achieved Engel class I designation at the 1-year follow-up, 6 of whom remained in class I at the latest follow-up.

CONCLUSIONS

This study analyzes one of the largest cohorts of pediatric patients who underwent awake craniotomy for maximal safe resection of tumor or epileptogenic lesions. For candidate patients, awake craniotomy is safe, feasible, and effective in carefully selected children.

Awake craniotomy with intraoperative stimulation mapping was pioneered by Wilder Penfield, who used this technique under nupercaine analgesia to guide resection for a 21-year-old patient with temporal lobe epilepsy.1,2 In the following years, Penfield evolved awake craniotomies for successful use in patients with cranial tumors and later included a combined regional and general anesthesia technique.3,4 Awake craniotomy with intraoperative neurophysiological mapping for maximal safe resection has become the widely accepted procedure for adult patients with supratentorial tumor or epileptogenic zones near eloquent cortex.5,6 This procedure inherently requires multidisciplinary collaboration between the neurosurgery, anesthesiology, and neuropsychology teams to ensure maximal safe resection while maintaining precautions against negative psychological experiences.

In children, awake craniotomies are less common because of concerns for compliance and potential psychological repercussions.79 Despite these concerns, successfully tolerated awake craniotomies have been reported in pediatric patients as young as 8 years of age with success rates comparable to those of adult patients.10,11 In the last 2 decades, attempts have been made to delineate eligibility criteria for pediatric patients, such as a minimum age. One review described eligible adult patients as having a high degree of cooperation and motivation, while ineligible patients have considerable anxiety, emotional instability, or inability to concentrate.12 In children, Trevisi et al. recommended a minimum age of 10 years for awake craniotomy for glioma resection.13 Despite this, several institutions have performed this procedure in patients younger than 10 years.8,10,14,15 Few institutions have implemented innovative protocols to address concerns of psychological difficulty that may exclude patients from awake craniotomy. Such protocols are directed toward preoperative exposure to the operating room and pre-, intra-, and postoperative involvement of Child Life Specialists implementing tailored intraoperative coping plans.16,17

Much of the current literature regarding awake craniotomy in children consists of case reports, emphasizing the need for larger case series and analyses from multiple years of surgical experience. To address this, we evaluated our institution’s 16-year history with insight regarding feasibility in children, evolution in intraoperative neuropsychology technique, and surgical outcomes.

Methods

Study Design

A retrospective chart review was completed for patients referred for awake craniotomy from January 2004 to March 2020 at Children’s Wisconsin in Milwaukee, Wisconsin. Patients were included if they were confirmed to have an attempted awake craniotomy and were younger than 18 years at the time of surgery. This study was approved by the Children’s Wisconsin institutional review board.

Outcomes

Primary outcomes included procedural feasibility, tolerance of awake testing, and preservation of functions tested. Feasibility was defined as completion of intraoperative awake testing with adequate resection of tumor or presumed epileptogenic zone. Tolerance, being the psychological ability to cooperate with intraoperative testing, was coded into 3 categories: 1) not tolerated: psychological symptoms (e.g., expressed anger, anxiety, distress) observed that prevented testing; 2) partially tolerated: psychological symptoms observed, yet testing was completed; or 3) fully tolerated: no psychological symptoms and testing was completed. Functions tested were categorized into 4 realms: language, motor, sensory, or visual, and were assessed at baseline, discharge after surgery, and the latest follow-up. The latest follow-up was defined as the most recent neurosurgery, neurology, neuropsychology, or oncology visit related to the primary presenting medical issue. Functional preservation was categorized as completely intact, mild transient impairment, mild permanent impairment, or major permanent impairment.

Secondary outcomes included presenting symptom, surgical location, anesthesia and skin-to-skin surgical time, lesion pathology, resection amount, Engel classification,18 Karnofsky Performance Scale (KPS) score,19 tumor progression/recurrence, and complications. Extent of resection was classified from postoperative imaging reports as gross-total resection (GTR) or subtotal resection (STR) for tumors.

Statistical Methods

All data were analyzed using descriptive statistics and frequencies.

Preoperative Clinical Evaluation

Candidacy evaluation included neuropsychological testing, functional MRI (fMRI), and discussion at the multidisciplinary epilepsy conference or neuro-oncology tumor board. Emphasis was placed on the neuropsychologist’s assessment of the patient’s temperament and theoretical tolerance of awake testing. The following factors were considered: maturity, cognitive status, anxiety, feasibility of alternative methods (evoked potentials, cortical mapping), tolerance of fMRI testing, and proximity of the proposed resection to eloquent brain.

If deemed an appropriate candidate, the patient underwent a neuropsychological evaluation including an age-appropriate variation of the Wechsler Intelligence Scales (WIS), measures of specific functions as appropriate (e.g., motor, language, visuospatial skills), and standardized assessment of emotional and behavioral functioning. Beginning in 2010, evaluations used standardized testing on tablet technology (NeuroMapper), with relevant paradigms selected based on the resection location. The NeuroMapper system presents a patient with stimuli on a patient-facing tablet of the two-iPad (Apple Inc.) interface while the neuropsychologist maneuvers task selection, delivery, and response verification using their examiner-facing tablet.20 Only stimuli on which the patient responds correctly and rapidly are selected for use intraoperatively. Areas of cognitive functioning for which testing paradigms exist include language, visuospatial abilities, memory, attention, and motor. The neuropsychologist who will be present during surgery coaches the patient on expectations for surgery.

A surgical strategy was devised regarding resection order with the goal of minimizing required awake testing time to prevent cognitive fatigue from compromising testing integrity. In most scenarios, there is only a portion of the resection that risks eloquent function. This portion of the resection should be done all at once, typically at the beginning or end of the operation.

Operative Technique

The awake craniotomy was divided into 3 procedural stages. The opening stage was defined as extending from administration of local anesthesia to the beginning of awake testing. The awake resection was the portion of the resection performed with the patient actively being tested in an awake state. Closure included the portion of the procedure following completion of the awake resection, including any noneloquent resection performed without active testing as well as closure of the craniotomy. While there is a requisite for patients to be awake during the resection stage, a variety of anesthesia options exist for opening and closure stages, including local anesthesia alone, monitored anesthesia care, and general anesthesia.

Historically, the first 4 procedures used an anesthesia approach common in adults. This involved light conscious sedation from the opening stage to the end of the awake portion of the resection. Anecdotally, patients experienced more pain and anxiety with this approach. Since 2014, the following protocol has been used at our institution.

Shortly after entering the operating room, monitored anesthesia care is administered with intravenous sedation and analgesia. The primary agents used for this opening stage are propofol, remifentanil, and dexmedetomidine. Typically, oxygen is administered via a nasal cannula throughout the procedure.

Considerable thought is given to patient positioning in a manner to allow for 1) appropriate surgical exposure; 2) line-of-sight access between the patient, neuropsychologist, and anesthesiologist; and 3) sufficient patient comfort (Fig. 1). There must be adequate space for the neuropsychologist and NeuroMapper tablets. Pin fixation is avoided when possible, as this can be an additional source of discomfort and anxiety when the patient is awake. Frameless stereotactic navigation is frequently used, typically electromagnetic, since pin fixation is seldom used.

FIG. 1.
FIG. 1.

A: Intraoperative testing with cortical stimulation. B: The same patient visualized from the anesthesia side during the procedure. C: Intraoperative neuropsychological testing with NeuroMapper programming presenting test stimuli to the patient during resection. Figure is available in color online only.

A local anesthesia mixture of 2% lidocaine HCl with 1:100,000 epinephrine, 0.5% bupivacaine, and 8.4% sodium bicarbonate is created in a 10:10:1 ratio for use prior to incision and as needed during the procedure (maximal dose 0.5 mL/kg). Depending on the craniotomy site, some or all major scalp sensory nerves (supratrochlear, supraorbital, auriculotemporal, zygomaticotemporal, greater and lesser occipital nerves) are blocked with local anesthesia prior to draping. Additional local anesthesia is applied to the planned incision and is injected as needed into the temporalis muscle and fascia during the procedure. A tuberculin needle can be used to inject between the leaves of the dura mater if there is pain related to dural retraction.

As the awake portion of the resection approaches, propofol and remifentanil are discontinued while dexmedetomidine may be discontinued or titrated as needed to maintain a calm but awake state. Cold saline is kept on hand in the event of a seizure. Intraoperative testing with the neuropsychologist using NeuroMapper algorithms then informs the surgeon’s approach during resection. After completion of the resection requiring active awake testing, a deeper level of anesthesia is targeted. This may be monitored anesthesia care or general anesthesia at the anesthesiologist’s discretion. If necessary, a laryngeal mask airway may be used to maintain the airway. If intraoperative MRI is used, inhalational agents are often given.

Intraoperative Neuropsychological Testing

Functions assessed during testing varied depending on the location of the planned resection. Tasks were selected based on presumed functionality of eloquent cortex within that region. Commonly, continuous testing of speech/language production, naming, and comprehension were performed if the intended resection was within the language-dominant hemisphere. Testing used informal and formal methodologies. In awake craniotomies prior to 2010, assessment was conducted by a pediatric neuropsychologist who engaged the patient in conversation and used formal stimuli interchangeably throughout the surgery with documentation of changes in speech articulation, comprehension or ability to respond to questions, and production of paraphasic errors (e.g., sound substitutions within words or replacement of intended word with other word). With the technology becoming available in 2010, intraoperative cognitive testing has become more systematic with the use of paradigms administered using NeuroMapper tablet technology, with each response captured (audio and video) and graded by the neuropsychologist to identify any change in function from baseline.

Results

Demographic and Clinical Data

An awake craniotomy was attempted in 11 patients, with 1 patient eventually receiving a repeat procedure, bringing the total procedure count to 12 (Table 1). The youngest patient was 11.5 years of age at the time of surgery, and the oldest patient was 17.9 years. Five patients had both tumors and associated epilepsy while the remaining 6 had tumors (n = 3) or epilepsy (n = 3) alone (Table 2). The most common presenting symptom was seizure in 9 patients (81.8%). Two awake resections were performed in the right hemisphere because the lesions were located within the perirolandic region (precentral gyrus, postcentral gyrus, paracentral lobule). The frontal lobe was the most common surgical location, with 5 procedures in the frontal lobe alone; 3 additional procedures involved the frontal lobe in addition to temporal (n = 1) or parietal (n = 2) lobes.

TABLE 1.

Patient-specific demographic and clinical data

Procedure No.Age at Op, yrsSexHandednessPresenting SymptomDiagnosisOp LocationHistopathology
116.92MLtSeizure, LUE weaknessTumorRt frontal, parietalGanglioglioma, low grade
212.50FRtSeizureTumor, epilepsyLt temporalOligodendroglioma, grade II
316.25MRtSeizureTumor, epilepsyLt temporalPilocytic astrocytoma, grade 1
4*11.50FRtSeizureTumor, epilepsyLt frontalGanglioglioma, grade 1, DNET
5*13.08FRtSeizureTumor, epilepsyLt frontalDNET
616.00FRtSeizureTumor, epilepsyLt frontalOligodendroglioma
717.92FRtHeadacheTumorLt frontal, parietalEpendymoma, grade II
814.50FLtSeizureEpilepsyLt frontalGliosis/encephalomalacia
917.33MRtSeizureEpilepsyLt temporalGliosis/encephalomalacia
1015.50MRtHeadache, double visionTumorRt parietalAstrocytoma, grade II
1116.42FRtSeizureEpilepsyLt frontal, temporalMild gliosis
1217.50FRtSeizureTumor, epilepsyLt frontalAstrocytoma, low grade

DNET = dysembryoplastic neuroepithelial tumor; LUE = left upper extremity.

The same patient, who underwent a repeat awake craniotomy.

TABLE 2.

Demographic variables of the cohort

Demographic VariableValue
Tumor-only diagnosis3 (27.3)
Epilepsy-only diagnosis3 (27.3)
Tumor & epilepsy diagnoses5 (45.5)
Mean patient age, yrs15.45 ± 2.02
Female8 (72.7)
Male3 (27.3)
Left-handed2 (18.2)
Right-handed9 (81.8)

Values are presented as the number of patients (%) or mean ± SD unless stated otherwise.

The first patient (procedure 1) underwent preoperative functional neuropsychological evaluation and did not undergo Wada testing for language localization, as the tumor was located in the right perirolandic region (precentral gyrus, postcentral gyrus, paracentral lobule). The second patient (procedure 2) underwent Wada testing during preoperative workup. The subsequent 9 patients successfully underwent preoperative fMRI. All 3 epilepsy-only patients underwent invasive intracranial monitoring with placement of stereotactic electroencephalography depth electrodes prior to awake craniotomy. One patient had nonlesional epilepsy (normal MRI) while the other two had multiple or diffuse abnormalities (herpes simplex encephalitis and perinatal intracerebral hemorrhages with subsequent encephalomalacia).

Primary Outcomes

Of the 12 attempted procedures, 11 were completed with resection of tumor, epileptogenic zone, or both. One procedure (procedure 1, Table 1) was aborted early in the operation due to bleeding; therefore, awake testing was not attempted (see Surgical Complications). One patient had a repeat awake craniotomy (procedure 5) 18 months after the first procedure.

Of the 11 procedures that involved attempted awake testing, 9 procedures (81.8%) were fully tolerated. Two patients partially tolerated awake testing. In the first case (procedure 6), a 16-year-old female awoke abruptly and exhibited signs of agitation prior to testing. The anesthesiologist resedated the patient and she awoke more gradually, and the resection proceeded with full testing cooperation. The second patient (procedure 11), a 16-year-old female, was occasionally tearful and sleepy during initial testing yet was consoled by the neuropsychologist and surgery continued for complete epileptogenic zone resection.

There were no permanent motor or language deficits after any procedure. One patient (procedure 8) demonstrated visuospatial reasoning and visuospatial/perceptual deficits postoperatively yet exhibited improved verbal/language skills at the 1-year follow-up neuropsychological evaluation. This was attributed to functional reorganization to the right hemisphere and/or discontinuation of topiramate.

Secondary Outcomes

Seizure Outcomes

Of the 8 patients with epilepsy, 7 patients were in Engel class I and 1 patient was in Engel class IIB at the 1-year follow-up (Table 3).

TABLE 3.

Surgical details and clinical outcomes at the latest follow-up time point

Clinical & Surgical VariablesValue
Surgical*
 Anesthesia time5 hrs 14 mins ± 1 hr 17 mins
 Skin-to-skin time3 hrs 46 mins ± 1 hr 11 mins
 Surgical location
  Lt hemisphere10 (83.3)
  Frontal lobe only5 (41.7)
  Temporal lobe only3 (25)
  Multilobar3 (25)
  Parietal lobe only1 (8.3)
 Functions tested during awake resection
  Language10 (90.9)
  Motor3 (27.2)
  Sensory1 (9.1)
 Resection amount per diagnosis
  Tumor only: GTR3
  Epilepsy only: entire proposed EZ2
  Epilepsy only: partial of proposed EZ1
  Tumor & epilepsy: entire proposed area2
  Tumor & epilepsy: STR proposed area4
Clinical§
 Engel classification total8
 Class I total6 (75)
  IA: complete seizure freedom2
  IB: seizure free + aura1
  ID: seizures w/ drug withdrawal only3
 Class II total2 (25)
  IIB: rare disabling seizures since op2
 KPS score total5
  100: no evidence of disease4 (80)
  90: minor symptoms of disease1 (20)

EZ = epileptogenic zone.

Values are presented as the number of procedures (%) or mean ± SD.

Two frontal/parietal and 1 frontal/temporal.

Percentages reflect the 11 procedures with awake testing of the 12 attempted procedures. Four patients had more than one function tested; therefore, percentages do not add up to 100.

Values are presented as the number of patients (%).

One patient with epilepsy had a repeat procedure (procedure 5) because of tumor progression. After the first procedure, the patient had a single breakthrough seizure 3 months postoperatively, wherein medication was then increased with no further seizures prior to the second awake procedure. After the second procedure, the patient experienced seizure in the setting of missed medication and was in Engel class ID at the latest follow-up. Another patient (procedure 2), initially in Engel class IA, experienced return of auditory seizures 5 years after resection and was therefore categorized in Engel class IIB at the latest follow-up. The other 5 patients remained at their 1-year Engel class I or II as of the latest follow-up visit, for a total of 6 patients with an Engel class I designation. All 3 patients with an epilepsy-only diagnosis were in Engel class I at the latest follow-up. Five patients in the entire cohort had medically refractory epilepsy. After awake craniotomy and as of the latest follow-up, 3 of these patients were in Engel class I (IA, IB, or ID), and the remaining 2 patients were in Engel class IIB.

Tumor Outcomes

Of the 8 awake craniotomies that involved tumor resection, 4 procedures were classified as GTRs. Four procedures were classified as STRs, 3 of which were limited by observed testing changes during resection (Table 3).

One instance of tumor progression was observed. The patient (procedure 4) with a WHO grade 1 ganglioglioma with a dysembryoplastic neuroepithelial tumor component and secondary epilepsy underwent an initial STR. The resection was limited by mild speech difficulty at the end of resection that resolved spontaneously with intact speech at the end of the procedure. Radiographic evidence of tumor progression was found 11 months postresection. The patient underwent a second awake craniotomy (procedure 5) for tumor resection 18 months after the first operation. The procedure was completed with residual tumor at the posteroinferior resection cavity borders and was similarly limited by mild intermittent paraphasic errors during intraoperative awake testing that spontaneously self-resolved. The patient has not had seizure or tumor progression and has not undergone adjuvant therapy as of the latest follow-up (57 months). Therefore, the patient was assigned a KPS score of 100. At the 1-year postoperative neuropsychological evaluation, the patient’s function was verified to be unchanged from baseline.

Two instances of tumor recurrence following GTR were observed. The first was observed in the patient with aborted awake surgery (procedure 1). After subsequent GTR of a WHO grade I ganglioglioma from the right precentral gyrus under general anesthesia, the patient’s seizures recurred 1 year later, and tumor recurrence was observed 2.5 years later. Following a second GTR, pathology revealed a WHO grade III anaplastic astrocytoma, which was treated with radiation therapy and temozolomide chemotherapy. Although seizures did not recur, the patient does have permanent left-sided weakness following the second resection. This patient has not experienced subsequent recurrence as of the latest follow-up (46 months). The second instance of recurrence occurred in a patient with a WHO grade II ependymoma (procedure 7) with observation of two enhancing nodules 17 months after GTR. Eighteen months after the first awake craniotomy, a repeat left frontal resection was completed without an awake component, as the recurrent resection was not felt to put eloquent brain at risk.

Neurological Deficits

There were three instances of transient neurological deficits. One patient experienced immediate postoperative difficulty repeating nonwords with impaired comprehension and paraphasic errors on visual naming tasks, which entirely resolved by hospital discharge. One patient experienced a mild sensory deficit of the left lower extremity after right parietal astrocytoma GTR, which resolved by postoperative day 10. The final patient exhibited two spells of dysarthric speech within the 1st week following surgery, without change in consciousness or word-finding abilities.

Neuropsychological Outcomes

Preoperative and postoperative evaluation scores are reported in Table 4. Selected candidates had reasonably intact cognitive skills within the broad average range, low levels of baseline anxiety, and adequate emotional maturity. Of the scores from the anxiety/depression measure of the Child Behavior Checklist, only one patient had a borderline clinical score (93rd–97th percentile). This patient did not express any psychological or emotional symptoms during intraoperative testing. No psychological sequelae were noted at any follow-up or referrals to psychiatry placed. No patient demonstrated a significant decline (> 0.5 SD) in any domain following surgery.

TABLE 4.

Neuropsychological testing scores

Testing MeasureScoreTime PointNo. of PatientsMean ± SDMedianRange
Full Scale IQ*Standard scorePreop792.3 ± 9.09876–102
Postop693.3 ± 16.691.570–117
General Ability Index*Standard scorePreop798.7 ± 15.59973–120
Postop495.3 ± 19.39272–125
Boston Naming TestRaw scorePreop949.6 ± 5.65136–57
Postop647.5 ± 10.75126–50
Child Behavior Checklist: anxiety/depression measureT-scorePreop851.3 ± 1.75150–80
Postop555.4 ± 14.65043–84

Full Scale IQ and General Ability Index scores were taken from the age-appropriate edition of the Wechsler Scales available at the time of the evaluation and included the Wechsler Intelligence Scale for Children–III (WISC-III), WISC-IV, and Wechsler Adult Intelligence Scale.

Surgical Complications

Two complications occurred. One took place in the procedure that did not reach awake testing (procedure 1, well-circumscribed tumor in the precentral gyrus), where surgeons encountered unanticipated epidural bleeding on bone flap elevation. Surgical focus shifted to hemostasis, and resection was deferred. Retrospectively, it appeared that the patient had an anomalous venous drainage system involving cortical veins draining into enlarged diploic veins that in turn drained into the superior surface of the superior sagittal sinus. At discharge, there was transient worsening of left upper-extremity weakness, which resolved by the time of resection under general anesthesia 2 months later.

The second complication (procedure 12) was a Propionibacterium acnes infection that occurred after resection of a low-grade astrocytoma. The infection was successfully treated with antibiotics and bone flap replacement with titanium mesh.

Discussion

Outcomes

This study evaluated one of the largest single-institution cohorts of pediatric patients undergoing awake craniotomies. We report a procedure completion feasibility of 92%, comparable to the 96% feasibility found in the University of Toronto’s pediatric cohort and 91% feasibility in the Medical University of Vienna’s pediatric cohort.8,21 In a recent meta-analysis of 50 pediatric awake craniotomies, only 2 procedures (4%) were aborted due to significant patient anxiety or failure to cooperate.14 In our series, only 1 procedure required intubation with conversion to deep sedation after unanticipated epidural bleeding was encountered, unrelated to the level of anesthesia.

All patients returned to baseline motor and language function. A recent pediatric case series reported that all patients retained language function and were seizure free at 4.3 years of follow-up.21 Notably, 6 of the 8 patients (75%) in our series with seizures prior to surgery were in Engel class I at the latest follow-up (Table 3). Similarly, a 2021 study reported 71% of adult patients as being in Engel class I and 29% in Engel class II at 6 years postcraniotomy for focal cortical dysplasia.22 Comparatively, a 2009 report of pediatric patients with preoperative seizures and tumors near eloquent cortex reported Engel class I outcomes in 49.1% following awake craniotomy.23

Ten procedures were fully tolerated and 2 were partially tolerated; one case involved emotional lability and the other involved patient agitation, although both patients completed necessary intraoperative testing to guide resection. This is consistent with evidence that both intravenous and inhalational anesthesia may lead to agitation and emotional lability on awakening.24 No patients were subsequently diagnosed with a psychological disorder or reported long-standing detrimental effects attributed to awake surgery. This finding agrees with the reports by Riquin et al. of no postoperative diagnoses of anxiety or trauma-related disorders and a 2019 review that did not find postoperative psychological sequelae related to awake surgery.14,25

Determining Candidacy

At our institution, pediatric neuropsychologists have the primary role in determining a patient’s ability to tolerate an awake craniotomy. This recommendation is made by the neuropsychologist who performs the baseline evaluation. The neuropsychologist is also privy to the results of fMRI and also performs the baseline preparation with the patient prior to surgery. There was no change in the approach to determination of eligibility or suitability for an awake craniotomy, which remained based on understanding of the individual’s level of cognitive functioning and their psychological status (e.g., baseline anxiety). A study by Kelm et al. found that awake craniotomies that involved neuropsychologists were associated with a higher frequency of GTR, shorter operative time, and a lower rate of unexpected residual tumor.26

All patients who underwent preoperative fMRI successfully completed and tolerated testing paradigms. This might suggest that successful fMRI during preoperative evaluation may have some degree of association with awake craniotomy tolerance. There may be overlap between patient characteristics that relate to the successful completion of fMRI testing and awake craniotomy, including cooperation, attentiveness, low anxiety, and the ability to remain still.27,28 There are similar characteristics that could exclude patients from fMRI and awake procedures, such as impaired motor, visual, auditory, or language function; decreased attention regulation; and neurodevelopmental disorders.27,28 Therefore, there may be clinical utility of fMRI testing as a low-stakes procedure to evaluate a patient’s emotional tolerance of the physical restraints of testing and ability to cooperate with paradigms. At our institution, no patient who cannot tolerate an fMRI scan is seriously considered for awake craniotomy.

The mean age of our cohort was approximately 15 years, and the youngest patient was 11.5 years. Anecdotally, younger patients performed well compared with older patients. In the case of the patient who underwent an additional procedure, she was more cooperative and calmer during the initial surgery at age 11 years compared with the subsequent procedure at age 13 years. We believe that patient candidacy should be based on thorough presurgical neuropsychology evaluation, demonstrated ability to perform tasks during fMRI, and a consensus opinion at multidisciplinary conference review, rather than using an age requirement.

Keys to Success

There are several key elements that we recommend for successful awake brain surgery in children (Table 5). As previously mentioned, careful patient selection is critical. Potters and Klimek emphasized the importance of a strong physician-patient relationship established prior to surgery to combat potential psychological sequelae and to focus intraoperatively on reducing emotional stress, fear, and pain that may evolve during the awake phase.29 We would add the importance of a strong neuropsychologist-patient relationship and a teamwork approach between surgeon, anesthesiologist, and neuropsychologist. The patient should have familiarity with the testing procedure, and baseline function should be established preoperatively. Patient positioning should be done thoughtfully with emphasis on comfort and access to the patient by neuropsychology and anesthesia. Aggressive use of local anesthesia and familiarity with scalp blocks is recommended. Keeping local anesthesia on hand for troubleshooting pain complaints during the procedure is essential. A surgical plan that minimizes the time spent with the patient actively testing will put less stress on the patient and surgical team. Efficient testing algorithms should be tailored to the eloquent brain at risk. The treating team should be facile at troubleshooting and be able to redirect the surgical or anesthetic approach as needs arise.13

TABLE 5.

Considerations for pediatric awake craniotomies

StageConsiderations
Preop
  • Neuropsychologist to evaluate candidacy for awake craniotomy in terms of cognition & emotional regulation

  • Selection of testing paradigms relevant to resection area

  • Establish rapport w/ neuropsychologist who will be present during intraoperative awake testing

  • Patient preparation w/ surgical workflow & testing paradigms

  • Surgical strategy geared toward minimizing awake testing time

  • Anesthesia team w/ experience in awake surgeries

Intraop
  • Aggressive use of local anesthesia including scalp blocks

  • Clear line of sight btwn patient & anesthesiologist, neuropsychologist, & tablet computer

  • Close physiological & emotional monitoring by neuropsychologist & anesthesia team

  • Avoidance of cranial pins

  • Additional local anesthesia on surgical field

  • Asleep-awake-asleep anesthetic strategy

  • Avoidance of excessive dural retraction

  • Limit awake period to portion of resection in or near eloquent tissue

Our practice has evolved to no longer use cranial pin fixation for awake surgeries. Rigid fixation can certainly be performed with local anesthetic at the pin sites, yet we have had concerns about the fixation as a source of pain or anxiety. We have found pin fixation to be unnecessary with the use of an electromagnetic frameless navigation system (Medtronic StealthStation). Two patient trackers are available for this system. The noninvasive tracker attaches to the patient’s scalp with adhesive. This modality requires positional planning such that the tracker is not vulnerable to scalp shifts relative to the skull during draping or exposure. If a higher degree of precision is required, the skull-mounted patient tracker is placed through a small separate incision following a scalp block. This method provides similar accuracy to optical frameless navigation with the added benefit of not requiring camera line of sight.

Limitations and Future Areas of Exploration

Because of the retrospective nature of the data, this study is subject to inherent limitations of all smaller retrospective cohort studies, such as observer bias and insufficient power to evaluate predictors of success. The retrospective nature limits evaluation to only those patients who underwent an attempted awake craniotomy and does not allow comparison with patients who were considered for, but ultimately denied, awake surgery. It is also quite possible that our patient selection was too stringent, and more patients could have benefited from awake surgery, as this study is insufficient to evaluate an error in this direction. Future areas of investigation could include the prospective development of metric-based criteria for awake surgery with prospective metrics for evaluating tolerance, as well as outcomes on those patients deemed ineligible for awake surgery. This would likely require a multi-institutional effort given the relatively low volume at a single institution.

Conclusions

This study presents one of the largest single-center cohorts of pediatric patients who underwent awake craniotomy for maximal safe resection of tumors or epileptogenic foci. We have found awake craniotomy to be safe, feasible, and effective in carefully selected patients.

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Contributions

Conception and design: Lew. Acquisition of data: Reecher, Koop, Awad, Kaufman. Analysis and interpretation of data: Lew, Reecher, Kim. Drafting the article: Reecher, Koop, Awad. Critically revising the article: Lew, Reecher, Koop, Awad, Kim, Foy, Kaufman. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Lew. Statistical analysis: Reecher. Administrative/technical/material support: Meier. Study supervision: Awad. Specialty consulting: Meier.

Supplemental Information

Previous Presentations

Portions of this work were presented as an e-poster at the 2020 AANS Annual Scientific Meeting, Boston, Massachusetts, April 25, 2020.

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    Kim SS, McCutcheon IE, Suki D, et al. Awake craniotomy for brain tumors near eloquent cortex: correlation of intraoperative cortical mapping with neurological outcomes in 309 consecutive patients. Neurosurgery. 2009;64(5):836-845,345-346.

    • PubMed
    • Search Google Scholar
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    Panditrao MM, Panditrao MM, Fernandes AJ, Gill GS. A study of psycho-behavioral patterns in patients emerging from general anesthesia using sevoflurane, propofol and their combination in early, intermediate and late post-operative period: a randomized controlled trial. Anesth Essays Res. 2013;7(2):257262.

    • PubMed
    • Search Google Scholar
    • Export Citation
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    Riquin E, Dinomais M, Malka J, et al. Psychiatric and psychologic impact of surgery while awake in children for resection of brain tumors. World Neurosurg. 2017;102:400405.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Kelm A, Sollmann N, Ille S, Meyer B, Ringel F, Krieg SM. Resection of gliomas with and without neuropsychological support during awake craniotomy—effects on surgery and clinical outcome. Front Oncol. 2017;7:176.

    • PubMed
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  • 27

    Johnson CA, Garnett EO, Chow HM, Spray GJ, Zhu DC, Chang SE. Developmental factors that predict head movement during resting-state functional magnetic resonance imaging in 3–7-year-old stuttering and non-stuttering children. Front Neurosci. 2021;15:753010.

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    Jones JY, Selvaraj B, Ho ML. Pediatric functional neuroimaging: practical tips and pearls. AJR Am J Roentgenol. 2020;214(5):9951007.

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    Potters JW, Klimek M. Awake craniotomy: improving the patient’s experience. Curr Opin Anaesthesiol. 2015;28(5):511516.

  • Collapse
  • Expand

Illustration from Caklili et al. (pp 223–235). © Savas Ceylan, published with permission.

  • FIG. 1.

    A: Intraoperative testing with cortical stimulation. B: The same patient visualized from the anesthesia side during the procedure. C: Intraoperative neuropsychological testing with NeuroMapper programming presenting test stimuli to the patient during resection. Figure is available in color online only.

  • 1

    Penfield W, Boldrey E. Somatic motor and sensory representation in the cerebral cortex of man as studied by electrical stimulation. Brain. 1937;60(4):389443.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Penfield W, Flanigin H. Surgical therapy of temporal lobe seizures. AMA Arch Neurol Psychiatry. 1950;64(4):491500.

  • 3

    Penfield W. Combined regional and general anesthesia for craniotomy and cortical exploration. Part I. Neurosurgical considerations. Int Anesth Clin. 1986;24(3):111.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Pasquet A. Combined regional and general anesthesia for craniotomy and cortical exploration. Part II. Anesthetic considerations. Int Anesth Clin. 1986;24(3):1220.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Ojemann G, Ojemann J, Lettich E, Berger M. Cortical language localization in left, dominant hemisphere. An electrical stimulation mapping investigation in 117 patients. J Neurosurg. 1989;71(3):316326.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    De Benedictis A, Moritz-Gasser S, Duffau H. Awake mapping optimizes the extent of resection for low-grade gliomas in eloquent areas. Neurosurgery. 2010;66(6):10741084.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Delion M, Terminassian A, Lehousse T, et al. Specificities of awake craniotomy and brain mapping in children for resection of supratentorial tumors in the language area. World Neurosurg. 2015;84(6):16451652.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Alcaraz García-Tejedor G, Echániz G, Strantzas S, et al. Feasibility of awake craniotomy in the pediatric population. Paediatr Anaesth. 2020;30(4):480489.

  • 9

    Milian M, Luerding R, Ploppa A, et al. "Imagine your neighbor mows the lawn": a pilot study of psychological sequelae due to awake craniotomy: clinical article. J Neurosurg. 2013;118(6):12881295.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Riquin E, Martin P, Duverger P, Menei P, Delion M. A case of awake craniotomy surgery in an 8-year-old girl. Childs Nerv Syst. 2017;33(7):10391042.

  • 11

    Szántó D, Gál J, Tankó B, et al. Pediatric neuroanesthesia—a review of the recent literature. Curr Anesthesiol Rep. 2022;12:467475.

  • 12

    Santini B, Talacchi A, Casagrande F, et al. Eligibility criteria and psychological profiles in patient candidates for awake craniotomy: a pilot study. J Neurosurg Anesthesiol. 2012;24(3):209216.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Trevisi G, Roujeau T, Duffau H. Awake surgery for hemispheric low-grade gliomas: oncological, functional and methodological differences between pediatric and adult populations. Childs Nerv Syst. 2016;32(10):18611874.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Lohkamp LN, Mottolese C, Szathmari A, et al. Awake brain surgery in children-review of the literature and state-of-the-art. Childs Nerv Syst. 2019;35(11):20712077.

  • 15

    Ratha V, Sampath N, Subramaniam S, Kumar VRR. Technical considerations in awake craniotomy with cortical and subcortical motor mapping in preadolescents: pushing the envelope. Pediatr Neurosurg. 2021;56(2):171178.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Labuschagne J, Lee CA, Mutyaba D, Mbanje T, Sibanda C. Awake craniotomy in a child: assessment of eligibility with a simulated theatre experience. Case Rep Anesthesiol. 2020;2020:6902075.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    McDowell MM, Ortega Peraza D, Abel TJ. Development and implementation of a novel child life protocol to enhance psychosocial support for pediatric awake craniotomies: technical note. Neurosurg Focus. 2020;48(2):E5.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Wieser HG, Blume WT, Fish D, et al. ILAE Commission Report. Proposal for a new classification of outcome with respect to epileptic seizures following epilepsy surgery. Epilepsia. 2001;42(2):282286.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Karnofsky DA, Burchenal JH. The clinical evaluation of chemotherapeutic agents in cancer. In: MacLeod CM, ed.Evaluation of Chemotherapeutic Agents. Columbia University Press;1949:191-205.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Sabsevitz DS, Middlebrooks EH, Tatum W, Grewal SS, Wharen R, Ritaccio AL. Examining the function of the visual word form area with stereo EEG electrical stimulation: a case report of pure alexia. Cortex. 2020;129:112118.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Herta J, Winter F, Pataraia E, et al. Awake brain surgery for language mapping in pediatric patients: a single-center experience. J Neurosurg Pediatr. 2022;29(6):700710.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Minkin K, Gabrovski K, Karazapryanov P, et al. Awake epilepsy surgery in patients with focal cortical dysplasia. World Neurosurg. 2021;151:e257e264.

  • 23

    Kim SS, McCutcheon IE, Suki D, et al. Awake craniotomy for brain tumors near eloquent cortex: correlation of intraoperative cortical mapping with neurological outcomes in 309 consecutive patients. Neurosurgery. 2009;64(5):836-845,345-346.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Panditrao MM, Panditrao MM, Fernandes AJ, Gill GS. A study of psycho-behavioral patterns in patients emerging from general anesthesia using sevoflurane, propofol and their combination in early, intermediate and late post-operative period: a randomized controlled trial. Anesth Essays Res. 2013;7(2):257262.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Riquin E, Dinomais M, Malka J, et al. Psychiatric and psychologic impact of surgery while awake in children for resection of brain tumors. World Neurosurg. 2017;102:400405.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Kelm A, Sollmann N, Ille S, Meyer B, Ringel F, Krieg SM. Resection of gliomas with and without neuropsychological support during awake craniotomy—effects on surgery and clinical outcome. Front Oncol. 2017;7:176.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Johnson CA, Garnett EO, Chow HM, Spray GJ, Zhu DC, Chang SE. Developmental factors that predict head movement during resting-state functional magnetic resonance imaging in 3–7-year-old stuttering and non-stuttering children. Front Neurosci. 2021;15:753010.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Jones JY, Selvaraj B, Ho ML. Pediatric functional neuroimaging: practical tips and pearls. AJR Am J Roentgenol. 2020;214(5):9951007.

  • 29

    Potters JW, Klimek M. Awake craniotomy: improving the patient’s experience. Curr Opin Anaesthesiol. 2015;28(5):511516.

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