Clinical Neurology and Neurosurgery 130 (2015) 140–149

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Intraoperative neurophysiological monitoring for intradural extramedullary tumors: Why not? Reza Ghadirpour a,b , Davide Nasi c,∗ , Corrado Iaccarino a,b , David Giraldi d , Rossella Sabadini e , Luisa Motti e , Francesco Sala f , Franco Servadei a,b a

Neurosurgery-Neurotraumatology Unit, Emergency Department, University Hospital of Parma, Parma, Italy Neurosurgery Unit, Neuromotor Department, IRCCS “Arcispedale Santa Maria Nuova” of Reggio Emilia, Reggio Emilia, Italy c Clinic of Neurosurgery, Department of Neurological Sciences, Polytechnic University of Marche, Umberto I General Hospital, Ancona, Italy d Department of Neurosurgery, Queen Elizabeth University Hospital, Birmingham, UK e Neurophysiology Unit, Neuromotor Department, IRCCS “Arcispedale Santa Maria Nuova” of Reggio Emilia, Reggio Emilia, Italy f Pediatric Neurosurgery, Institute of Neurosurgery, University Hospital of Verona, Verona, Italy b

a r t i c l e

i n f o

Article history: Received 9 November 2014 Received in revised form 15 December 2014 Accepted 3 January 2015 Available online 12 January 2015 Keywords: Intradural extramedullary tumors Intraoperative neurophysiological monitoring Somatosensory evoked potentials Motor evoked potentials D-waves

a b s t r a c t Background: While intraoperative neurophysiological monitoring (IOM) for intramedullary tumors has become a standard in neurosurgical practice, IOM for intradural extramedullary tumors (IDEMs) is still under debate. The aim of this study is to evaluate the role of IOM during surgery for IDEMs. Methods: From March 2008 to March 2013, 68 patients had microsurgery with IOM for IDEMs (31 schwannomas, 25 meningiomas, 6 ependymomas of the cauda/filum terminalis, 4 dermoid cysts and 2 other lesions). The IOM included somatosensory evoked potentials (SEPs), motor evoked potentials (MEPs), and – in selected cases – D-waves. Also preoperative and postoperative neurophysiological assessment was performed with SEPs and MEPs. All patients were evaluated at admission and at follow up (minimum 6 months) with the Modified McCormick Scale (mMCs). Results: Three different IOM patterns were observed during surgery: no change in evoked potentials (63 cases), transitory evoked potentials change (3 cases) and loss of evoked potentials (2 cases). In the first setting surgery was never stopped and a radical tumor removal was achieved (no stop surgery group). In 3 cases of transitory evoked potentials change, surgery was temporarily halted but the tumors were at the end completely removed (stop and go surgery group). In 2 more patients the loss of evoked potentials led to an incomplete resection (stop surgery group). No patients presented a worsening of the pre-operative clinical conditions (at admission 47 patients presented mMCs 1–2 and 21 patients mMCs 3–5, while at follow up 62 patients are mMCS 1–2 and 6 patients mMCs 3–5). Conclusions: In our series significant IOM changes occurred in 5 out of 68 patients with IDEMs (7.35%), and it is conceivable that the modification of the surgical strategy – induced by IOM – prevented or mitigated neurological injury in these cases. Vice versa, in 63 patients (92.65%) IOM invariably predicted a good neurological outcome. Furthermore this technique allowed a safer tumor removal in IDEMs placed in difficult locations as cranio-vertebral junction or in antero/antero-lateral position (where rotation of spinal cord can be monitored) and even in case of tumor adherent to the spinal cord without a clear cleavage plane. © 2015 Elsevier B.V. All rights reserved.

1. Introduction The tumors found in the intradural extramedullary compartment are: meningiomas, nerve sheath tumors (schwannomas and neurofibromas), metastases, dermoid tumors, teratomas, paragangliomas, ependymoma of the cauda equina or filum terminalis and

∗ Corresponding author. Tel.: +39 0521704666; fax: +39 0521704634. E-mail address: [email protected] (D. Nasi). http://dx.doi.org/10.1016/j.clineuro.2015.01.007 0303-8467/© 2015 Elsevier B.V. All rights reserved.

hemangioblastomas [1]. They represent 30% of all spinal tumors [2]. The most common primitive intradural extramedullary tumors are meningiomas and nerve sheath tumors (schwannomas and neurofibromas) [3]. Intradural extramedullary tumors (IDEMs) are treatable and the surgical goal is a total resection [1]. Intraoperative neurophysiological monitoring (IOM) may be valuable to achieve a radical resection during surgery for IDEMs in two ways. Firstly by confirming the physiological integrity of neural pathways during uneventful procedures. Secondly, by detecting a neurological injury in time for

R. Ghadirpour et al. / Clinical Neurology and Neurosurgery 130 (2015) 140–149 Table 1 Modified McCormick Scale (mMCs) for neurological evaluation of patients with IDEL. Modified McCormick Scale (mMCs) Grade

Definition

I

Neurologically intact, ambulates normally, may have minimal dysesthesia Mild motor or sensory deficit, patient maintains functional independence Moderate deficit, limitation of function, independent w/external aid Severe motor or sensory deficit, limit of function w/a dependent patient Paraplegic or quadriplegic, even if there is flickering movement

II III IV V

corrective measures to be taken, before an irreversible damage occurs [4]. In 1937, Penfield and Boldrey published a paper [5] about the systematic exploration of the cerebral cortex establishing the conditions for the development of IOM. After Penfield, except for the use of neuromonitoring in epilepsy surgery, almost half a century passed without significant developments in the IOM. In 1972 the somatosensory evoked potentials (SEPs) were introduced by Nash and his group to assess the functional integrity of the spinal cord during surgery [6]. However, according to the first report published in 1986 by Lesser et al. [7], several studies reported cases of postoperative para- or tetraparesis/plegia despite SEPs preservation [8,9]. These studies showed the inability of SEPs in monitoring the anterolateral column, typically damaged in patients with anterior spinal artery syndrome. In 1990s the introduction of motor evoked potentials (MEPs) elicited by transcranial electrical stimulation (TES) for monitoring of corticospinal motor pathway has dramatically improved the IOM value and reliability. The combined use of epidurally recorded D wave and motor evoked potentials from limb muscles has proved to be a valuable predictor of post-operative motor outcome in patients harboring intramedullary spinal cord tumors (ISCTs) [10,11]. In this regard, a few studies on ISCTs surgery have shown that the loss of muscle MEPs in the presence of a D-wave preserved up to 50% of its baseline amplitude, will result in only transient motor deficits [10,11]. The use of IOM during surgery for ISCT has become a standard [4,12,13]. Vice versa, the utility of IOM for IDEMs has not yet been clearly confirmed [14]. The aim of our study is to assess the usefulness of IOM in the treatment of IDEMs. To the best of our knowledge, no studies have been undertaken so far focused only on the use of IOM for IDEMs.

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Table 2 General data, tumors location, preoperative neurophysiological evaluation and Modified McCormick grade on admission. General data, lesion location, preoperative neurophysiological evaluation and modified McCormick grade on admission Age (years) Average (range) Gender Male Female Total

57.2 (17–80) n (%) 23 (33.83%) 45 (66.17%) 68

Lesions location (N %) Skull-Cervical Junction Cervical Thoracic Lumbar Total

n (%) 5 (7.35%) 11 (16.18%) 37 (54.42%) 15 (22.05%) 68

Preoperative SEPs–MEPs (N %) Normal Pathological Total

n (%) 12 (14.65%) 56 (82.35%) 68

Modified McCormick grade on admission I II III IV V Total

n (%) 20 (29.41%) 27 (39.70%) 18 (26.47%) 2 (2.94%) 1 (1.48%) 68

an assessment of the mMCs grade, as well as a neurophysiologic evaluation with SEPs and MEPs. 2.2. Intraoperative neurophysiological monitoring (IOM) Our standardized protocol for IOM includes: preoperative, intraoperative and postoperative SEPs and MEPs, intraoperative Dwaves (in cervical and thoracic lesions), electromyography (EMG) and bulbocavernosus reflex for cauda or filum terminalis procedures. For stimulation and recording, the ISIS system was used (Inomed Co., Emmendingen, Germany). During surgery IOM was subdivided into: post-induction baseline, intraoperative period and closure. A brief description of our protocol follows. 2.2.1. SEPs SEPs were elicited by stimulation of the median nerve at the wrist and the posterior tibial nerve at the ankle (intensity, 40 mA; duration, 0.2 ms; repetition rate, 4.3 Hz). Recordings were ensured via corkscrew-like (CS) electrodes inserted in the scalp at Cz/Fz (legs) and C3/C4/Fz (arms), according to the international 10–20 system of electrode placement.

2. Methods 2.1. Patient population From March 2008 to March 2013 clinical and IOM data of 68 patients presenting with IDEMs were prospectively collected in a data base and retrospectively analyzed. Neurological status on admission and at follow-up was assessed using the Modified McCormick Scale (Table 1) [15]. Sex, age, Modified McCormick Scale (mMCs) on admission, preoperative neurophysiological evaluation with SEPs and MEPs and tumors localization are summarized in Table 2. The pain was the most common presenting symptom among patients with IDEMs (51%), followed by gait ataxia (18%), motor weakness (12%), sensory deficits (8%) and sphincter disturbances (2%). The diagnosis of IDEMs was performed for all patients by magnetic resonance imaging (MRI) study (1.5 Tesla), with and without contrast. At the follow-up, all patients had a post-operative MRI,

2.2.2. MEPs and D-wave As described previously in literature [17,18], TES with multi pulse technique was used to elicit muscle MEPs and a single TES stimulus was applied to elicit a D-wave. TES with multi pulse technique includes short trains of 5 square-wave stimuli (single pulse duration, 0.5 ms; interstimulus interval, 4 ms, at a rate of 2 Hz) through CS electrodes placed at C1/C2 (lower limb) and C3/C4 (upper limbs) scalp sites, according to the 10–20 system. A constant current stimulator with a maximum output of 200 mA was applied. MEPs were recorded via needle electrodes inserted into upper and lower extremity muscles. We usually monitor muscle MEPs from the abductor pollicis brevis and the extensor digitorum longus for superior limbs and the vastus lateralis, tibialis anterior and the abductor hallucis for inferior limbs. D-wave was monitored in patients harboring tumors in the cervical and thoracic spine. A single TES stimulus of 0.5 ms duration was applied to elicit a D-wave, recorded by an electrode placed in the epidural or

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subdural space cranial and caudal to the tumor, after laminectomy. The electrode cranial to the tumor serves as a control recording, to discriminate whether or not an intraoperative neurophysiological event is related to surgical maneuvers or general influences such as anesthesia or cardiovascular factors [5]. The electrode we use is FSR-03 (Inomed Co., Emmendingen, Germany). 2.3. Surgical procedure and interpretation of IOM: no stop surgery, stop and go surgery and stop surgery On the basis of data published in literature [10,11,16–18], the following IOM criteria were used to adjust the surgical strategy: - A persistent amplitude loss of at least 50% of cortical SEPs was used as warning criteria. - A persistent mMEPs loss were considered significant and surgery temporary stopped; however the surgeon was warned if there were persistent amplitude decrements of more than 50% of baseline values. - A decrease of more than 50% of the baseline amplitude for D-wave was considered a warning criteria. Whenever these warning thresholds were reached, after excluding technical issues and systemic changes (blood pressure, body temperature and the partial pressure of CO2 ), the surgery was temporary stopped. At this point any hypotensions was corrected and the surgical field was irrigated with warm saline solution to facilitate recovery of the evoked potentials. In selected cases, papaverine was locally instilled to improve cord perfusion [11,17,18]. If, following these corrective measures a recovery of IOM (even partial) was seen, surgery was resumed and a complete tumor removal was attempted (stop and go surgery). If the significant alterations of Dwave or mMEPs loss did not resolve following corrective measures, lesion removal was abandoned to prevent permanent neurological damage (stop surgery). Surgery was never abandoned on the basis of minor changes and without attempts to start again. The extent of resection was evaluated intraoperatively and at radiological followup with MRI. 3. Results Surgical removal, results of IOM, histological findings and variation of mMCs at follow-up (minimum 6 months) were reported in Table 3. Monitorable D-waves was achieved in all cervical and thoracic intradural lesions (53), except in three patients with severe neurological deficits before surgery (respectively two with mMCs IV and one with V). SEPs and MEPs monitoring could be performed in all patients. The overall monitor ability was 97.1%, where at least 1 of the 3 modalities was applicable in 68 surgical procedures. Gross total resection could be achieved in 66 (97.05%) and partial resection in 2 (2.95%) patients. In the group of gross total resection, we observed 3 cases (4.41%) of “stop and go surgery” (significant alterations of the IOM with recovery after temporarily halting surgery) in two cases for cervical and dorsal meningiomas and in one case for thoracic schwannoma. In two other patients (2.95%) MEPs were lost and the D-wave permanently dropped by about 50%. After several attempts to start again, surgery was definitively abandoned (stop surgery). These patients harbored respectively a T10 schwannoma and T7–T8 solitary fibrous tumors. In these cases we were forced to leave a small part of the tumor attached to the spinal cord. Both patients showed a transient mild neurological deterioration after surgery. However at follow-up (respectively at 4 years and a 6 months) we observe at least a recovery of pre-operative neurological status. MRI examination of both patients showed no tumor recurrence. In the others 63 patients (92.65%) IOM invariably

Table 3 Surgical results, results of intraoperative neurophysiological monitoring, histological results and Modified McCormick grade at follow-up (minimum 6 months). Surgical results, results of intraoperative SEPs/MEPs, results of D-WAVE, histological results and modified McCormick grade at follow-up Surgical results Gross total resection Stop and go surgery Partial resection Stop surgery Total

n (%) 66 (97.05%) 3 (4.41%) 2 (2.94%) 2 (2.94%) 68

Results of Intraoperative SEPs/MEPs Present with/without minor changes Decrease of amplitude > 50% or lost unilaterally or bilaterally Total

n (%) 63 (92.64%) 5 (7.35%)

Results of D-WAVE Unchanged or decreased less than 50% Decreased more than 50% Unmonitorablea Total Histological results Schwannoma Meningioma Ependymoma cauda/filum Dermoid cyst Solitary fibrous tumor Total

n (%) 46 (67.65%) 4 (5.88%) 18 (26.47%) 68 n (%) 31 (45.60%) 25 (36.76%) 6 (8.82%) 4 (5.88%) 2 (2.94%) 68

Modified McCormick grade at follow-up I II III IV V Total

n (%) 48 (70.58%) 14 (20.58%) 4 (5.88) 1 (1.48%) 1 (1.48%) 68

68

a Monitorable D-waves was achieved in all cervical and thoracic intradural lesions (53), except in three patients with severe neurological deficits before surgery (respectively two with mMCs IV and one with V). SEPs and MEPs monitoring could be performed in all patients.

predicted a good neurological outcome. Characteristics of patients presenting IOM changes during tumor resection are summarized in Table 4. The average preoperative score of mMCs was 2.11 while at follow-up was 1.31. Variation of mMCS at follow-up (minimum 6 months), as compared with before surgery, was reported in Table 5. Regarding postoperative complications in our series we observed one case of extradural hematoma that not required surgical intervention. In this case there was no permanent neurological deficits. In our series we did not observe any postoperative instability of the spine and we had no postoperative mortality. 3.1. Illustrative case 1 (no stop surgery) A 59-year-old woman was admitted to our department after 1 week history of progressive left hemiparesis quantifiable in 3/5, according to Medical Research Council Scale for Motor Strength (MRC) and dysphagia. Cervical MRI image revealed an extensive left intradural extramedullary tumor with contrast enhancement at C0–C2 with compression of the cervico-medullary junction (Fig. 1 A and B). On admission he was classified as mMCs 3. Preoperative electrophysiological examination showed a slight prolongation of the central motor conduction time. IOM was carried out according to the protocol described above. A C1–C2 left hemilaminectomy (laterally extended with vertebral artery identification with micro Doppler ultrasound) was performed with minimally sub-occipital craniotomy in a three-quarter prone position. Gross total resection of the tumor was achieved (Fig. 1C–F). During the whole procedure D-wave and SEPs remained unchanged and muscle MEPs showed an overall improvement. The postoperative course was

Table 4 Characteristics of patients presenting intraoperative neurophysiological monitoring changes during tumor resection. Age (yr)/Sex

Location

mMCS admission/preoperative deficit (MRC)

IOM changes

IOM recovery

Action taken

Extent of resection

Post-operative deficit

Histological results

mMCs at follow-up (time)/deficit at follow-up (MRC)

Recurrence or growth of residual at follow-up MRI (time)

1

59/F

T10

III Paraparesis (MRC 3/5)

Bil SEPs loss

No

Stop surgery

Partial

Worsening paraparesis (MRC 2/5)

Schwannoma

IFull recovery of strength in LL [40 months]

No (40 months)

Yes

Stop and go surgery

Total

Unchanged

Schwannoma

II partial recovery of strength in LL (MRC 4/5) [6 months]

No (6 months)

No

Stop surgery

Partial

Worsening paraparesis (MRC 3/5)

Solitary Fibrous Tumor

III recovery of pre-op neurological status (MRC 4/5) [1 year]

No (1 year)

Yes

Stop and go surgery

Total

Unchanged

Schwannoma

I Full recovery of right arm’s strength [22 months]

No (22 moths)

Yes

Stop and go surgery

Total

Transient worsening of paraparesis (MRC 3/5)

Meningioma

I Full recovery of strength in LL (40 months)

No (8 months)

2

3

4

78/F

35/M

68/M

T12

T7-T8

C4-C5

III bilateral deficit of ileopsoas and quadriceps (MRC 3/5)

II Slight paraparesis (MRC 4/5)

II Slight arm Paresis (MRC 4/5)

Bil LL MEPs loss D-Wave decreased by 50% Bil SEPs > 50% Bil LL MEPs loss D-Wave decreased by 50% Unil SEPs loss Bil LL MEPs loss D-Wave decreased by 50% Unil SEPs decreased by 50% Unil SP MEPs loss

5

61/M

T5

II Slight paraparesis (MRC 4/5)

D-Wave decreased by 50% Bil SEPs loss Bil LL MEPS loss

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Pt

D-Wave stable mMCs, Modified McCormick Scale; MRC, Medical Research Council Scale for Motor Strength (graded 1–5); LL, lower limbs; SL, superior limbs; Bil, bilateral; Unil, Unilateral.

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Fig. 1. (A,B) Preoperative coronal and axial T1-weighted postgadolineum magnetic resonance (MRI) images demonstrating an extensive intradural extramedullary tumor with contrast enhancement at C0–C2 and compression of the bulb medulla junction. (C) Intraoperative findings, just after durotomy, of extramedullary lesion compatible with meningioma (M), cerebellar tonsils (CT). (D) Before removal of tumor, we proceeded with identification of bulbo-medullary junction (BMJ) and vertebral artery (VA) also with the aid of micro Doppler ultrasound. (E) After generous debulking, we started the deafferentation of the tumor, near C1 spinal roots (C1R). (F) At the end, the tumor was completely removed and spinal cord decompressed. (G,H) Postoperative sagittal and T1-weighted postgadolineum MRI Images 6 months after surgery confirming complete tumor removal.

Fig. 2. (A,B) Preoperative sagittal T2-weighted and axial T1-weighted postgadolineum MRI images demonstrating a double intradural extramedullary lesion at T11 and T12. The lesion at the level of T12 was larger and determined spinal cord compression with intra and extra-canalar extension. (C–F) Pre-operative neurophysiological studies showed pathological alterations of SEPs and MEPs of inferior limbs.

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Fig. 3. (A,B) Postoperative sagittal T2-weighted and axial T1-weighted postgadolineum MRI Images 6 months after surgery showed gross total resection of T12 lesion. (C) Postoperative SEPs superior limbs (normal). (D) Postoperative SEPs left inferior limb (normal). (E) Postoperative SEPs right inferior limb (increased latency). (F) Postoperative slight reduction of right vastus medialis MEP

uncomplicated and at discharge the patient showed complete neurologic recovery. Histological examination was positive for atypical meningioma WHO II. Postoperative MRI image at 6 months confirmed total resection (Fig. 1 G and H). After a follow-up of 13 months, the patient has resumed full independence in normal activities and a normal neurological exam (mMCs 1). 3.2. Illustrative case 2 (stop and go surgery) In the second case, a 78-year-old woman presented at our department after a 1-month history of low back pain and progressive weakness in the lower limbs. The neurological examination Table 5 Variation of Modified McCormick grade at follow-up (minimum 6 months) after surgery. Modified McCormick grade on admission

Modified McCormick grade at follow-up

Grade

n (%)

Grade

n (%)

I II III IV V Total

20 (29.41%) 27 (39.70%) 18 (26.47%) 2 (2.94%) 1 (1.48%) 68

I II III IV V Total

48 (70.58%) 14 (20.58%) 4 (5.88) 1 (1.48%) 1 (1.48%) 68

demonstrated bilateral weakness of ileopsoas and quadriceps (MRC 3/5) and she was unable to walk independently (mMCs 3). Spinal MRI scans revealed a double intradural extramedullary lesion at T11 and T12. The lesion at the level of T12 was larger and determined spinal cord compression with intra and extracanalar extension (Fig. 2 A and B). For this reason it was decided to treat initially only this lesion to shorten the operating time since the patient had severe comorbidities (chronic obstructive pulmonary disease and heart failure). Preoperative SEPs and MEPs were pathological (Fig. 2C–F). After L1–T11 laminectomy an epidural catheter for monitoring of the D-wave was placed above and below the lesion. The placement of electrode below the T10 bony level often does not allow to record a D wave of sufficient amplitude (due to a lack of enough numbers of CT fibers at this level) [18], but in this case we were able to record a reliable D-wave. During tumor removal MEPs from lower limbs disappeared and D-Wave amplitude decreased more than 50%. For this reason, surgery was temporarily stopped and corrective measures were taken, such as warm irrigation. After 10 min DWave amplitude returned to values over 50% and muscle MEPs reappeared, allowing the removal of the entire intradural intracanalar component of the lesion (stop and go surgery). Immediately after surgery, the patient’s paraparesis did not change. Postoperative neurophysiological examination revealed slight reduction of right vastus medialis MEP and increased latency of right

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Fig. 4. (A,B) Preoperative sagittal and axial T1-weighted postgadolineum MRI images demonstrating an intradural and extra-axial T10 lesion occupying the whole canal with contrast enhancement, (C) Postoperative sagittal T1-weighted postgadolineum MRI Image 6 months after surgery revealed minimal residual lesion without spinal cord compression. (D) Axial T1-weighted postgadolineum magnetic resonance MRI image at 4 years showed essentially unchanged size of the residual neuroma located at T10.

inferior limb SEPs (Fig. 3 C–F). Histological examination revealed a schwannoma (WHO I). At a follow-up evaluation 6 months after surgery, the neurological examination of the patient demonstrated partial recovery of strength both in right (MRC 4/5) and left leg (MRC 4/5) and the patient was able to walk without support (mMCs 2). A MRI showed complete removal of the T12 schwannoma (Fig. 3 A and B). A second surgery for removal of the neuroma at T11 was then performed one year after the first operation. 3.3. Illustrative case 3 (stop surgery) The third case concerns a 59-year-old woman with a 3-months history of low back pain, gait difficulty, weakness and numbness in the lower limbs. Neurological examination revealed diffuse proximal weakness in the left and right leg (MRC 3/5). Spinal MRI imaging revealed an intradural extra-axial T10 tumor occupying the whole canal. The spinal cord appeared displaced and compressed (Fig. 4 A and B). Preoperative neurophysiological studies pointed out SEPs and MEPs pathological alterations. She underwent a T9–T11 laminectomy and D-Wave above and below the level of the lesion

was recorded through epidural electrodes. After opening the dura, the lesion appeared strongly adherent to the spinal cord without a clear cleavage plane. During the initial internal debulking of the tumor, there was a reduction in the right tibial SEP. However, the MEPs remained stable, and we decided to keep on with the resection. When approximately 75% of the resection was completed, D-Wave decreased by 50% and MEPs disappeared (Fig. 5 A and B). Once technical or systemic issues were quickly excluded, surgery was stopped. In spite of several attempts to resume surgery, the persistence of changes in D-Wave amplitude and MEPs, prompted the surgeon to give up with resection. We were forced to abandon the surgery leaving a small residual tumor. The histological diagnosis was schwannoma. Immediately after surgery the patient showed a worsening of lower-extremity strength (MRC 2/5). At discharge the patient presented initial recovery of strength in lower limbs (MRC 4/5). At 6-month follow-up, the MRI examination revealed minimal residual lesion without spinal cord compression (Fig. 4C). The patient had full neurological recovery and went back to her previous occupation. Her gait was normal. The radiological follow-up at 40 months showed no growth of residual tumor (Fig. 4D).

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Fig. 5. (A) Inferior D-wave (under the lesion) amplitude declined throughout the critical part of the procedure by more than 50% of baseline (thick black arrows). (B) At the same time MEPs of lower limbs were suddenly lost during tumor removal. After excluding technical problems (clots on the surface of the electrodes to be solved by washing with physiological solution, decrease systemic blood pressure, vascular spasm, hypothermia) we immediately suspended the operation. Since the neurophysiological parameters have not returned to acceptable levels, it was decided to abandon the surgery leaving a small residual tumor. Sup.: superior; Inf.: inferior; VastL.: left vastus lateralis; T.A.L.: left tibialis anterior; AbdhL: left abductor hallucis; VastR.: right vastus lateralis; T.A.R.: right tibialis anterior; AbdhR.: right abductor hallucis.

4. Discussion Many studies have investigated the sensitivity and specificity of IOM for a variety of spinal surgeries. A large prospective study conducted by Sutter et al. [19] evaluated the prognostic value of multimodality monitoring in patients undergoing surgery for spinal stenosis, deformities, and spinal tumors. The authors of this study reported a sensitivity of 89% and a specificity of 99% in the detection of postoperative neurological deficits. Recently, other papers have assessed the predictive value of IOM for postoperative neurological deficits. Among these, Nuwer et al. [20] classified 604 studies according to the evidence-based methodology of the American Academy of Neurology, of which 40 reached the inclusion criteria. Twenty-eight works were subsequently excluded because they contained data of class III or IV. Processing was therefore restricted to 4 class I papers and 8 class II papers. All studies examined confirmed that persistent changes of IOM correlated with additional deficit. The authors concluded that the IOM has proven to be reliable in predicting an increased risk of postoperative paraparesis, paraplegia and tetraplegia. In case of important IOM changes the surgical team should therefore be alerted about a possible risk of adverse postoperative outcomes, in order to take appropriate countermeasures. In 2010 a meta-analysis by Fehlings et al. examined 103 papers, of which 32 reached the inclusion criteria. The authors conclude that there is a high level of evidence that the IOM is sensitive and specific in identifying an intraoperative spinal cord damage, even if there are not enough elements to demonstrate that it can reduce the incidence of worsening or of new postoperative deficit. On the basis of the sensitivity and specificity of IOM, the use of the same is

recommended in spine surgery where the spinal cord or nerve roots are deemed to be at risk, including procedures involving deformity correction and procedures that require the placement of instrumentation [21]. Another meta-analysis [22] of 187 publications, of which 18 reached the requirements identified in advance, concludes that the use of IOM allows a more aggressive approach for surgery of ISCT and scoliosis surgery [22]. Although Class I evidence supporting the use of IOM in ISCT and scoliosis surgeries is lacking, IOM during these forms of spinal surgery is currently accepted as standard of care [4,12,13,23]. As well described by Sala et al., the level of evidence for the benefits of IOM for ISCT surgery is limited to class II and class III studies because in the field of ISCT surgery a prospective randomized study in which patients are randomized and assigned to a control group or a monitored group would be unethical and unacceptable both for patient and surgeon [24]. Furthermore, it should be recognized that the same level of evidence is applied to most of our clinical practice within the field of neurosurgery. In another paper, Sala et al. tried to address the question concerning the real impact of IOM for ISCT by comparing the neurological outcome of 50 patients operated on with the assistance of IOM (SEPs, MEPs, and D-wave) with that of 50 patients selected from 301 intramedullary spinal cord tumors surgery previously operated on by the same team without IOM. This study conclude that a combined MEPs and D-wave monitoring protocol significantly improves motor outcome at a follow-up of at least 3 months [11]. On the contrary, the use of IOM for intradural extramedullary tumors (IDEMs) is still under debate [14]. In 2008 Sandalcioglu et al. reported in a paper their singleinstitution review of 131 spinal meningiomas surgically treated with only SEPs. At the last follow-up the neurological state was

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improved or unchanged in 126 patients (96.2%) and worse in 4 patients (3%) [25]. In the authors’ opinion, these data show that good clinical outcomes could be reached without the use of sophisticated monitoring. Similarly, several other studies on surgery of IDEMs were conducted without the aid of the IOM [26–28]. In the last 20 years, there has been a growing interest to the IOM as evidenced by the increase in studies reported in the literature. However, most IOM studies concerns surgery for scoliosis and surgery of ISCT. On the contrary, there are no specific studies about the use of IOM for IDEMs surgery. Some papers reported limited experience on the role of IOM for spine/spinal cord surgeries including IDETs. Sutter et al. in 2007 presented the use of IOM in 109 patients undergoing spinal surgery and among these 41 harbored IDEMs [29]. Two other studies report, within their experience in the use of IOM for spinal/spinal tumor surgery, respectively 45 and 55 cases of IDEMs [14,30]. Recently, Forster et al. presented a study of 203 patients harboring spinal tumor and surgically treated with the help of IOM. 141 patients had IDEMs (78 meningiomas, 49 schwannomas, 8 hemangiopericytoma and 6 metastasis) [31]. In these studies significant alteration of the IOM that changed the surgical strategy (with benefit to the patient) ranged between 5.67% and 17.7%. In our single-center experience, over the past 5 years, the incidence of significant IOM changes during surgery for IDEMs was 5 out of 68 patients (7.35%). It remains disputable what would have been the outcome of these five patients should the surgeon not have been alerted of warning IOM signals or should him not have reacted to these warnings. Yet, in the light of the robust evidence of IOM being a good predictor of an increased risk for postoperative paresis, we believe that proceeding with the surgery would have exposed those patients to a significant risk of neurological injury [20]. Also in some cases, as illustrative case 1, the use of IOM allowed a safer complete tumor removal in a complicated location and in antero-lateral position (where rotation of spinal cord can be monitored). In our experience the IOM were useful in surgery of intradural lesions that have a high degree of vascularization from the arachnoid or are adherent to the spinal cord without a clear cleavage plane, as in illustrative case 3. Our series of IDEMs surgically treated with IOM is the largest reported after the series published by Forster et al. This retrospective study is not focused on IDEMs surgery but is aimed to show the importance of monitoring throughout the entire surgical procedure including laminotomy, dura opening, tumor removal, duroplasty and laminoplasty. The limitations of our study include the retrospective nature of the study (even if the data base is prospectively collected), the absence of randomization and a lack of comparative group with removal of these tumors without monitoring. The IOM was anyway conducted by the same team during all the years and all operations were performed by senior surgeon (R.G. and F.S.), limiting one of the possible sources of bias. 5. Conclusions In our series significant IOM changes occurred in 5 out of 68 patients with IDEMs (7.35%), and it is conceivable that the modification of the surgical strategy – induced by IOM – prevented or mitigated neurological injury in these cases. Vice versa, in 63 patients (92.65%) IOM invariably predicted a good neurological outcome. Then the use of the IOM during surgery for IDEMs in our and others series was useful in approximately 5–17% of patients [14,29–31]. Furthermore this technique allowed a safer tumor removal in IDEMs placed in difficult locations as cranio-vertebral junction or in antero/antero-lateral position (where rotation of spinal cord can be monitored) and even in case of tumor adherent to the spinal cord without a clear cleavage plane.

Conflict of interest This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Acknowledgments The authors wish to thank Dr. Antonio Romano and Dr. Salvatore Ippolito, Neurosurgery-Neurotraumatology Unit, Emergency Department, University Hospital of Parma and Neurosurgery Unit, Neuromotor Department, IRCCS “Arcispedale Santa Maria Nuova” of Reggio Emilia, for their essential contribution in surgery of the entire series reported. The authors are grateful to Dr. Gabriella Torre, Dr. Francesca Ferrari and Dr. Claudio Basile, Neurophysiology Unit, Neuromotor Department, IRCCS “Arcispedale Santa Maria Nuova” of Reggio Emilia, for technical help in monitoring the patients and for helping with the collection of data. References [1] Joaquim AF, Almeida JP, dos Santos MJ, Ghizoni E, de Oliveira E, Tedeschi H. Surgical management of intradural extramedullary tumors located anteriorly to the spinal cord. J Clin Neurosci 2012;19:1150–3. [2] Van Goethem JWM, van den Hauwe L, Özsarlak Ö, De Schepper AM, Parizel PM. Spinal tumors. Eur J Radiol 2004;50:159–76. [3] Helseth A, Sverre JM. Primary intraspinal neoplasms in Norway, 1955–1986. J Neurosurg 1989;71:842–5. [4] Sala F, Bricolo A, Faccioli F, Lanteri P, Gerosa M. Surgery for intramedullary spinal cord tumors: the role of intraoperative (neurophysiological) monitoring. Eur Spine J 2007;16(Suppl. 2):S130–9. [5] Penfield W, Boldrey E. Somatic motor and sensory representation in the cerebral cortex of man as studied by electrical stimulation. Brain 1937;60:389–443. [6] Nash CL, Brodkey JS, Croft TJ. A model for electrical monitoring of spinal cord function in scoliosis patients undergoing correction (abstract). J Bone Joint Surg 1972;54:197–8. [7] Lesser RP, Raudzens PA, Luders H, Nuwer MR, Goldie WD, Morris HH, et al. Postoperative neurological deficits may occur despite unchanged intraoperative somatosensory evoked potentials. Ann Neurol 1986;19:22–5. [8] Zornow MH, Grafe MR, Tybor C, Swenson MR. Preservation of evoked potentials in a case of anterior spinal artery syndrome. Electroencephalogr Clin Neurophysiol 1990;77:137–9. [9] Pelosi L, Jardine A, Webb JK. Neurological complications of anterior spinal surgery for kyphosis with normal somatosensory evoked potentials (SEPs). J Neurol Neurosurg Psychiatry 1999;66:662–4. [10] Kothbauer KF, Deletis V, Epstein FJ. Motor-evoked potential monitoring for intramedullary spinal cord tumor surgery: correlation of clinical and neurophysiological data in a series of 100 consecutive procedures. Neurosurg Focus 1998;4:1–9. [11] Sala F, Palandri G, Basso E, Lanteri P, Deletis V, Faccioli F, et al. Motor evoked potential monitoring improves outcome after surgery for intramedullary spinal cord tumors: a historical control study. Neurosurgery 2006;58:1129–43. [12] Hsu W, Bettegowda C, Jallo GI. Intramedullary spinal cord tumor surgery: can we do it without intraoperative neurophysiological monitoring? Childs Nerv Syst 2010;26:241–5. [13] Yanni DS, Ulkatan S, Deletis V, Barrenechea IJ, Sen C, Perin NI. Utility of neurophysiological monitoring using dorsal column mapping in intramedullary spinal cord surgery. J Neurosurg Spine 2010;12:623–8. [14] Costa P, Peretta P, Faccani G. Relevance of intraoperative D wave in spine and spinal cord surgeries. Eur Spine J 2013;22:840–8. [15] McCormick PC, Torres R, Post KD, Stein BM. Intramedullary ependymoma of the spinal cord. J Neurosurg 1990;72:523–32. [16] MacDonald DB, Al-Zayed Z, Stigsby B, Al-Homoud I. Median somatosensory evoked potential intraoperative monitoring: recommendations based on signal-to-noise ratio analysis. Clin Neurophysiol 2009;120(2):315–28. [17] Deletis V, Kothbauer K. Intraoperative neurophysiology of the corticospinal tract. In: Stalberg E, Sharma HS, Olsson Y, editors. Spinal cord monitoring. Vienna: Springer-Verlag; 1998. [18] Deletis. Intraoperative neurophysiological monitoring of the spinal cord during spinal cord and spine surgery: a review focus on the corticospinal tracts. Clin Neurophysiol 2008;119:248–64. [19] Sutter M, Eggspuehler A, Muller A, Dvorak J. Multimodal intraoperative monitoring: an overview and proposal of methodology based on 1017 cases. Eur Spine J 2007;16(Suppl. 2):S153–61. [20] Nuwer MR, Emerson RG, Galloway G, Legatt AD, Lopez J, Minahan R, et al. Evidence-based guideline update: Intraoperative spinal monitoring with somatosensory and transcranial electrical motor evoked potentials. Neurology 2012;78:585–9.

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