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	':	Intraoperative Neurophysiological Monitoring for Extended Endonasal Approaches to the Skull Base: A Technical Guide
Harminder Singh, M.D.1, Robert M. Lober, M.D., Ph.D.1, Richard W. Vogel, Ph.D., D.ABNM2, Adam T. Doan, D.C., D.ABNM2, Craig I. Matsumoto, DHSc, D.ABNM, Tyler J. Kenning, M.D.3, James Evans, M.D.4

1Stanford Hospitals and Clinics, Department of Neurosurgery, 300 Pasteur Drive, Stanford, CA 94305
2Safe Passage Neuromonitoring, 915 Broadway, Suite 1200, New York, NY 10010
3Albany Medical Center Neurosurgery Group, 47 New Scotland Ave, MC 10, Physicians Pavilion, First Floor, Albany, NY 12208
4Thomas Jefferson University Hospital, Department of Neurosurgery, 909 Walnut Street, Third Floor, Philadelphia, PA 19107

Corresponding author:
Harminder Singh, MD
Stanford Hospitals and Clinics
Department of Neurosurgery
300 Pasteur Drive
Stanford, CA 94305
 HYPERLINK "mailto:Harmansingh.md@gmail.com" Harmansingh.md@gmail.com
(408)885-4646

Keywords: Intraoperative monitoring, extended endonasal approach, endoscopic, skull base surgery

Short title: Intraoperative monitoring for extended endonasal approaches

Disclosure: RWV and ATD are employees of Safe Passage Neuromonitoring, New York, NY.

Funding: None
Abstract 
Intraoperative monitoring of cranial nerve motor function during extended endonasal approaches to the skull base is both feasible and safe; however, its application during endonasal procedures is not well described in the literature. The authors report on a comprehensive, multimodal approach to monitoring the functional integrity of at-risk nervous system structures, including the cranial nerves, the corticospinal and corticobulbar tracts, the thalamocortical somatosensory system, and also the vascular perfusion of the cerebral cortex and brainstem, during endonasal surgery of the skull base. The modalities employed include spontaneous and electrically-triggered electromyography, transcranial electric motor evoked potentials, somatosensory evoked potentials, auditory evoked potentials, and electroencephalography. Methodological considerations, benefits and pitfalls are discussed. The authors argue that, while individual modalities have their limitations, multimodal neurophysiological monitoring provides a real-time, comprehensive assessment of nervous system function, and allows for safer, more aggressive management of skull base tumors via the endonasal route.

Introduction
For over a century in neurosurgery, the endonasal approach was recognized as a means to access sellar lesions. ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK  \l "_ENREF_1" \o "Hirsch, 1910 #81" 1-3] More recently, uses for the endonasal approach have dramatically expanded with the arrival of the endoscope and neuronavigation. The reach now is far beyond the sphenoid and sella to the entire ventral skull base via transcribiform, transplanum, transdorsum sellae, transclival, and transpterygopalatine fossa corridors. ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK  \l "_ENREF_4" \o "Cavallo, 2005 #77" 4-7] Multiple reports in the literature have demonstrated the utility of these approaches in reaching the anterior, middle, and infratemporal fossae, and thus a new working knowledge of anatomic relationships and multimodal monitoring is required to safely operate at these sites.
Global cortical monitoring with motor-evoked potentials, somatosensory-evoked potentials, and electroencephalography is likely to be helpful in situations where the internal carotid arteries or their branches are at risk. ADDIN EN.CITE <EndNote><Cite><Author>Sala</Author><Year>2007</Year><RecNum>50</RecNum><DisplayText>[8]</DisplayText><record><rec-number>50</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">50</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Sala, F.</author><author>Manganotti, P.</author><author>Tramontano, V.</author><author>Bricolo, A.</author><author>Gerosa, M.</author></authors></contributors><auth-address>Section of neurosurgery, department of neurological and visual sciences, university of Verona, piazzale Stefani 1, 37126 Verona, Italy. francesco.sala@azosp.vr.it</auth-address><titles><title>Monitoring of motor pathways during brain stem surgery: what we have achieved and what we still miss?</title><secondary-title>Neurophysiol Clin</secondary-title></titles><periodical><full-title>Neurophysiol Clin</full-title></periodical><pages>399-406</pages><volume>37</volume><number>6</number><edition>2007/12/18</edition><keywords><keyword>Animals</keyword><keyword>Brain Mapping</keyword><keyword>Brain Stem/*surgery</keyword><keyword>Efferent Pathways/*physiology</keyword><keyword>Evoked Potentials, Motor/physiology</keyword><keyword>Humans</keyword><keyword>Monitoring, Intraoperative/*methods</keyword><keyword>*Neurosurgical Procedures</keyword></keywords><dates><year>2007</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>0987-7053 (Print)&#xD;0987-7053 (Linking)</isbn><accession-num>18083495</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/18083495</url></related-urls></urls><electronic-resource-num>S0987-7053(07)00143-8 [pii]&#xD;10.1016/j.neucli.2007.09.013</electronic-resource-num><language>eng</language></record></Cite></EndNote>[ HYPERLINK  \l "_ENREF_8" \o "Sala, 2007 #50" 8]  In the case of skull base approaches, this includes exposure of the parasellar region and cavernous sinus. ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK  \l "_ENREF_9" \o "Thirumala, 2011 #42" 9]  Similarly, brainstem auditory evoked potentials are useful for detecting compromise at or around the vertebrobasilar junction, as is the case for transclival approaches. ADDIN EN.CITE <EndNote><Cite><Author>Little</Author><Year>1983</Year><RecNum>95</RecNum><DisplayText>[10]</DisplayText><record><rec-number>95</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">95</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Little, J. R.</author><author>Lesser, R. P.</author><author>Lueders, H.</author><author>Furlan, A. J.</author></authors></contributors><titles><title>Brain stem auditory evoked potentials in posterior circulation surgery</title><secondary-title>Neurosurgery</secondary-title></titles><periodical><full-title>Neurosurgery</full-title></periodical><pages>496-502</pages><volume>12</volume><number>5</number><edition>1983/05/01</edition><keywords><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Brain Stem/*physiopathology</keyword><keyword>*Cerebrovascular Circulation</keyword><keyword>*Evoked Potentials, Auditory</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Intraoperative Period</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Monitoring, Physiologic</keyword><keyword>Vascular Diseases/physiopathology/*surgery</keyword></keywords><dates><year>1983</year><pub-dates><date>May</date></pub-dates></dates><isbn>0148-396X (Print)&#xD;0148-396X (Linking)</isbn><accession-num>6866230</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/6866230</url></related-urls></urls><language>eng</language></record></Cite></EndNote>[ HYPERLINK  \l "_ENREF_10" \o "Little, 1983 #95" 10] 
Intraoperative monitoring of the oculomotor, trochlear, trigeminal (maxillary division), and abducens nerves with needle electrodes placed in the inferior rectus, superior oblique, masseter, and lateral rectus muscles, respectively, has long been used during transcranial approaches to the cavernous sinus. ADDIN EN.CITE <EndNote><Cite><Author>Sekhar</Author><Year>1986</Year><RecNum>25</RecNum><DisplayText>[11]</DisplayText><record><rec-number>25</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">25</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Sekhar, L. N.</author><author>Moller, A. R.</author></authors></contributors><titles><title>Operative management of tumors involving the cavernous sinus</title><secondary-title>J Neurosurg</secondary-title></titles><periodical><full-title>J Neurosurg</full-title></periodical><pages>879-89</pages><volume>64</volume><number>6</number><edition>1986/06/01</edition><keywords><keyword>Adenoma/*surgery</keyword><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Brain Neoplasms/*surgery</keyword><keyword>Cavernous Sinus/*surgery</keyword><keyword>Chondrosarcoma/*surgery</keyword><keyword>Chordoma/*surgery</keyword><keyword>Cranial Nerve Neoplasms/surgery</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Meningioma/*surgery</keyword><keyword>Middle Aged</keyword><keyword>Neurilemmoma/surgery</keyword><keyword>Trigeminal Nerve/surgery</keyword></keywords><dates><year>1986</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>0022-3085 (Print)&#xD;0022-3085 (Linking)</isbn><accession-num>3701438</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/3701438</url></related-urls></urls><electronic-resource-num>10.3171/jns.1986.64.6.0879</electronic-resource-num><language>eng</language></record></Cite></EndNote>[ HYPERLINK  \l "_ENREF_11" \o "Sekhar, 1986 #25" 11]  It is equally applicable in many extended endonasal approaches, including cases in which the cavernous sinus is not accessed. The oculomotor nerve is vulnerable in the interpeduncular cistern via the transsphenoidal ADDIN EN.CITE <EndNote><Cite><Author>Iaconetta</Author><Year>2010</Year><RecNum>82</RecNum><DisplayText>[12]</DisplayText><record><rec-number>82</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">82</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Iaconetta, G.</author><author>de Notaris, M.</author><author>Cavallo, L. M.</author><author>Benet, A.</author><author>Ensenat, J.</author><author>Samii, M.</author><author>Ferrer, E.</author><author>Prats-Galino, A.</author><author>Cappabianca, P.</author></authors></contributors><auth-address>Universita degli Studi di Napoli Federico II, Department of Neurological Sciences, Division of Neurosurgery, Naples, Italy.</auth-address><titles><title>The oculomotor nerve: microanatomical and endoscopic study</title><secondary-title>Neurosurgery</secondary-title></titles><periodical><full-title>Neurosurgery</full-title></periodical><pages>593-601; discussion 601</pages><volume>66</volume><number>3</number><edition>2010/02/23</edition><keywords><keyword>Cadaver</keyword><keyword>Endoscopy/*methods</keyword><keyword>Humans</keyword><keyword>Microsurgery/methods</keyword><keyword>Neuroanatomy/*methods</keyword><keyword>Oculomotor Nerve/*anatomy &amp; histology/*surgery</keyword></keywords><dates><year>2010</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1524-4040 (Electronic)&#xD;0148-396X (Linking)</isbn><accession-num>20173555</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/20173555</url></related-urls></urls><electronic-resource-num>10.1227/01.NEU.0000365422.36441.C8&#xD;00006123-201003000-00023 [pii]</electronic-resource-num><language>eng</language></record></Cite></EndNote>[ HYPERLINK  \l "_ENREF_12" \o "Iaconetta, 2010 #82" 12] and transplanum routes, ADDIN EN.CITE <EndNote><Cite><Author>Abuzayed</Author><Year>2010</Year><RecNum>75</RecNum><DisplayText>[13]</DisplayText><record><rec-number>75</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">75</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Abuzayed, B.</author><author>Tanriover, N.</author><author>Akar, Z.</author><author>Eraslan, B. S.</author><author>Gazioglu, N.</author></authors></contributors><auth-address>Department of Neurosurgery, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey. sylvius@live.com</auth-address><titles><title>Extended endoscopic endonasal approach to the suprasellar parachiasmatic cisterns: anatomic study</title><secondary-title>Childs Nerv Syst</secondary-title></titles><periodical><full-title>Childs Nerv Syst</full-title></periodical><pages>1161-70</pages><volume>26</volume><number>9</number><edition>2010/06/23</edition><keywords><keyword>Adult</keyword><keyword>Cranial Sinuses/*anatomy &amp; histology</keyword><keyword>Humans</keyword><keyword>Neuroendoscopy/*methods</keyword><keyword>Nose</keyword><keyword>Optic Chiasm/anatomy &amp; histology</keyword><keyword>Skull Base/*anatomy &amp; histology</keyword><keyword>Subarachnoid Space/*anatomy &amp; histology</keyword><keyword>Third Ventricle/*anatomy &amp; histology</keyword></keywords><dates><year>2010</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>1433-0350 (Electronic)&#xD;0256-7040 (Linking)</isbn><accession-num>20567834</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/20567834</url></related-urls></urls><electronic-resource-num>10.1007/s00381-010-1204-0</electronic-resource-num><language>eng</language></record></Cite></EndNote>[ HYPERLINK  \l "_ENREF_13" \o "Abuzayed, 2010 #75" 13] with vascular compromise possible from injury to the inferolateral trunk of the cavernous carotid or its branches. ADDIN EN.CITE <EndNote><Cite><Author>Iaconetta</Author><Year>2010</Year><RecNum>82</RecNum><DisplayText>[12]</DisplayText><record><rec-number>82</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">82</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Iaconetta, G.</author><author>de Notaris, M.</author><author>Cavallo, L. M.</author><author>Benet, A.</author><author>Ensenat, J.</author><author>Samii, M.</author><author>Ferrer, E.</author><author>Prats-Galino, A.</author><author>Cappabianca, P.</author></authors></contributors><auth-address>Universita degli Studi di Napoli Federico II, Department of Neurological Sciences, Division of Neurosurgery, Naples, Italy.</auth-address><titles><title>The oculomotor nerve: microanatomical and endoscopic study</title><secondary-title>Neurosurgery</secondary-title></titles><periodical><full-title>Neurosurgery</full-title></periodical><pages>593-601; discussion 601</pages><volume>66</volume><number>3</number><edition>2010/02/23</edition><keywords><keyword>Cadaver</keyword><keyword>Endoscopy/*methods</keyword><keyword>Humans</keyword><keyword>Microsurgery/methods</keyword><keyword>Neuroanatomy/*methods</keyword><keyword>Oculomotor Nerve/*anatomy &amp; histology/*surgery</keyword></keywords><dates><year>2010</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1524-4040 (Electronic)&#xD;0148-396X (Linking)</isbn><accession-num>20173555</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/20173555</url></related-urls></urls><electronic-resource-num>10.1227/01.NEU.0000365422.36441.C8&#xD;00006123-201003000-00023 [pii]</electronic-resource-num><language>eng</language></record></Cite></EndNote>[ HYPERLINK  \l "_ENREF_12" \o "Iaconetta, 2010 #82" 12] The trochlear nerve may be exposed at the ambiens division of the cisternal segment through the transellar transtubercular route, and ischemic injury may occur with injury to the superior cerebellar artery. ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK  \l "_ENREF_14" \o "Iaconetta, 2013 #83" 14] The trigeminal nerve may be violated in Meckel�s cave via the transpterygoid corridor. ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK  \l "_ENREF_15" \o "Kassam, 2009 #87" 15]
The abducens nerve, being the longest and most ventrally located cranial nerve at the level of the clivus and cavernous sinus, is particularly at risk during approaches to petroclival lesions via the midline transclival, paramedian suprapetrous, and medial petrous apex approaches. ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK  \l "_ENREF_16" \o "Barges-Coll, 2010 #76" 16] In these cases, the risk may be increased by abnormal anatomy, e.g., medial displacement of the nerve by a petroclival tumor or upward displacement by a cisternal mass. Similar to the oculomotor nerve, it may also suffer vascular compromise by injury to the inferolateral trunk from the cavernous segment of the internal carotid artery.
As endonasal approaches are extended to the inferior clivus, as well as through the transcondylar, and transjugular corridors, ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK  \l "_ENREF_17" \o "Morera, 2010 #88" 17] attention must be placed on low cranial nerve monitoring, including the glossopharyngeal, vagus, accessory, and hypoglossal nerves.
To date, the techniques of multimodal monitoring of cranial nerves, as they pertain to endoscopic endonasal skull base surgery, have not been well studied. We have found that, in particular among monitoring modalities, free-running electromyography (EMG) at cranial myotomes provides real-time feedback of cranial nerve function when operating near these sites. Recognition of nerve irritation during a procedure allows for a change in surgical strategy, with the caveat that procedures may be delayed by false positive responses unrelated to physical manipulation of a cranial nerve. In some cases, nerve stimulation is useful to avoid injury. 
Here we report the techniques most effectively used for intraoperative neurophysiological monitoring (IONM) during the extended endonasal approach to the skull base.
Methods 
IONM has been used during various surgical procedures for decades, gaining popularity in its modern form with the introduction of somatosensory evoked potentials for surgery in the 1970�s. ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK  \l "_ENREF_18" \o "Nash, 1977 #97" 18,  HYPERLINK  \l "_ENREF_19" \o "Tamaki, 2007 #32" 19]  In its evolution, IONM has expanded its scope and understanding, allowing it to be used effectively in myriad surgical procedures that include much of the central and peripheral nervous system. The goal of IONM is to reduce the risk of iatrogenic neural injury and to provide functional guidance to the surgical/anesthesia team, as necessary. This is based on the premise that the patient�s electrophysiology changes in a measureable way, prior to the onset of permanent neurological deficit. Thoughtful data trend analysis, a keen understanding of neural elements at risk for injury, and knowledge of surgical technique (time-locking data changes to surgical/anesthetic conditions) are all critical in the assessment of these measures. Iatrogenic injury is always one of the most feared complications of neurosurgery, and using the extended endonasal approach to reach pathology is no exception. Given the complex anatomy and physiology encountered in this approach, a multimodal monitoring plan is required to adequately assess the areas at risk, as well as to increase the sensitivity and specificity of the totality of the monitoring plan. Depending on the location of the pathology, we commonly use electroencephalography (EEG), free-running and stimulus-triggered EMG of muscles innervated by cranial nerves, somatosensory evoked potentials (SSEPs), motor evoked potentials (MEPs), and brainstem auditory evoked potentials (BAEPs) to ensure full coverage of at-risk neural structures (TABLE 1). Knowing the advantages and drawbacks of each modality is necessary for correct interpretation of response data. 
Electromyography:
Electromyography (EMG) is recorded in surgery to monitor somatic efferent nerve activity as well as assess the functional integrity of individual nerves. First introduced in the 1960s as a means to assess facial nerve function during exploratory parotid surgery, ADDIN EN.CITE <EndNote><Cite><Author>Parsons</Author><Year>1968</Year><RecNum>18</RecNum><DisplayText>[20]</DisplayText><record><rec-number>18</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">18</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Parsons, R. C.</author></authors></contributors><titles><title>Electrical nerve stimulation at surgery</title><secondary-title>Laryngoscope</secondary-title></titles><periodical><full-title>Laryngoscope</full-title></periodical><pages>742-8</pages><volume>78</volume><number>5</number><edition>1968/05/01</edition><keywords><keyword>*Electric Stimulation/instrumentation</keyword><keyword>*Facial Nerve</keyword><keyword>Parotid Gland/surgery</keyword></keywords><dates><year>1968</year><pub-dates><date>May</date></pub-dates></dates><isbn>0023-852X (Print)&#xD;0023-852X (Linking)</isbn><accession-num>5656952</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/5656952</url></related-urls></urls><electronic-resource-num>10.1288/00005537-196805000-00003</electronic-resource-num><language>eng</language></record></Cite></EndNote>[ HYPERLINK  \l "_ENREF_20" \o "Parsons, 1968 #18" 20]  EMG recording techniques were later adapted for intracranial, ADDIN EN.CITE <EndNote><Cite><Author>Delgado</Author><Year>1979</Year><RecNum>6</RecNum><DisplayText>[21]</DisplayText><record><rec-number>6</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">6</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Delgado, T. E.</author><author>Bucheit, W. A.</author><author>Rosenholtz, H. R.</author><author>Chrissian, S.</author></authors></contributors><titles><title>Intraoperative monitoring of facila muscle evoked responses obtained by intracranial stimulation of the facila nerve: a more accurate technique for facila nerve dissection</title><secondary-title>Neurosurgery</secondary-title></titles><periodical><full-title>Neurosurgery</full-title></periodical><pages>418-21</pages><volume>4</volume><number>5</number><edition>1979/05/01</edition><keywords><keyword>*Electromyography</keyword><keyword>Evoked Potentials</keyword><keyword>Facial Nerve/physiopathology/*surgery</keyword><keyword>Humans</keyword><keyword>Methods</keyword><keyword>Neuroma, Acoustic/physiopathology/*surgery</keyword></keywords><dates><year>1979</year><pub-dates><date>May</date></pub-dates></dates><isbn>0148-396X (Print)&#xD;0148-396X (Linking)</isbn><accession-num>460569</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/460569</url></related-urls></urls><language>eng</language></record></Cite></EndNote>[ HYPERLINK  \l "_ENREF_21" \o "Delgado, 1979 #6" 21] spinal, ADDIN EN.CITE <EndNote><Cite><Author>Hormes</Author><Year>1993</Year><RecNum>7</RecNum><DisplayText>[22]</DisplayText><record><rec-number>7</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">7</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hormes, J. T.</author><author>Chappuis, J. L.</author></authors></contributors><auth-address>Atlanta Orthopaedic Group, Georgia.</auth-address><titles><title>Monitoring of lumbosacral nerve roots during spinal instrumentation</title><secondary-title>Spine (Phila Pa 1976)</secondary-title></titles><periodical><full-title>Spine (Phila Pa 1976)</full-title></periodical><pages>2059-62</pages><volume>18</volume><number>14</number><edition>1993/10/15</edition><keywords><keyword>Adult</keyword><keyword>Cauda Equina/injuries/*physiology</keyword><keyword>Electromyography/methods</keyword><keyword>Evoked Potentials, Somatosensory/*physiology</keyword><keyword>Humans</keyword><keyword>*Internal Fixators</keyword><keyword>Intraoperative Complications/prevention &amp; control</keyword><keyword>Lumbar Vertebrae/*surgery</keyword><keyword>Male</keyword><keyword>Monitoring, Intraoperative/*methods</keyword><keyword>*Spinal Fusion</keyword></keywords><dates><year>1993</year><pub-dates><date>Oct 15</date></pub-dates></dates><isbn>0362-2436 (Print)&#xD;0362-2436 (Linking)</isbn><accession-num>8272960</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/8272960</url></related-urls></urls><language>eng</language></record></Cite></EndNote>[ HYPERLINK  \l "_ENREF_22" \o "Hormes, 1993 #7" 22] and peripheral nerve surgeries. ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK  \l "_ENREF_23" \o "Kline, 1969 #9" 23] A large body of the literature devoted to EMG use during intracranial surgery is devoted to facial nerve monitoring in the cerebellopontine angle, ADDIN EN.CITE <EndNote><Cite><Author>Yingling</Author><Year>1992</Year><RecNum>31</RecNum><DisplayText>[24]</DisplayText><record><rec-number>31</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">31</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Yingling, C. D.</author><author>Gardi, J. N.</author></authors></contributors><auth-address>Department of Neurological Surgery, University of California School of Medicine, San Francisco.</auth-address><titles><title>Intraoperative monitoring of facial and cochlear nerves during acoustic neuroma surgery</title><secondary-title>Otolaryngol Clin North Am</secondary-title></titles><periodical><full-title>Otolaryngol Clin North Am</full-title></periodical><pages>413-48</pages><volume>25</volume><number>2</number><edition>1992/04/01</edition><keywords><keyword>Cochlear Nerve/physiology</keyword><keyword>Electric Stimulation/instrumentation</keyword><keyword>Electroencephalography</keyword><keyword>Electromyography</keyword><keyword>Evoked Potentials, Auditory, Brain Stem/physiology</keyword><keyword>Facial Nerve/physiology</keyword><keyword>Humans</keyword><keyword>Monitoring, Intraoperative/*methods</keyword><keyword>Neuroma, Acoustic/*physiopathology/*surgery</keyword><keyword>Treatment Outcome</keyword></keywords><dates><year>1992</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0030-6665 (Print)&#xD;0030-6665 (Linking)</isbn><accession-num>1630836</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/1630836</url></related-urls></urls><language>eng</language></record></Cite></EndNote>[ HYPERLINK  \l "_ENREF_24" \o "Yingling, 1992 #31" 24]  but there is a paucity of reports on the use of this technique with the extended endonasal approach to the skull base. With this approach, EMG recordings are particularly important to identify cranial nerves and guide tumor resection when the pathology involves the cavernous sinus or retroclival regions. While other techniques used in multimodal IONM provide valuable information about nervous system function, EMG is the only method that can 1) provide real-time feedback about neural activation throughout the course of surgery, 2) accurately detect and localize motor or mixed motor-sensory nerves embedded within tumor, and 3) reliably assess the integrity of cranial nerve motor functions before, during and after tumor resection. 
The basic premise of EMG is that depolarization of a motor nerve produces a recordable electrical potential within one or more muscle(s) innervated by that particular nerve. This activity is recorded using subdermal or intramuscular needle electrodes. A bipolar montage is frequently employed, consisting of two active recording leads placed within the same muscle. The signal is amplified (50-100 �V), band-pass filtered (30-1500 Hz) and displayed on a computer screen in real time. Accurate interpretation of EMG is facilitated by simultaneous visual and auditory monitoring, so a speaker is used in parallel to provide concurrent auditory feedback. Whereas incidental (spontaneous) motor cranial nerve activity is monitored with a free-running EMG recording, stimulus-triggered EMG recordings are time-locked to delivery of an electrical pulse and used to map the location of cranial motor nerves, as well as assess their functional status, as described below.
Free-running EMG is recorded throughout the course of the surgery and it provides real-time feedback whenever a nerve is activated. Several distinct firing patterns of spontaneous EMG (sEMG) activity may be recorded, ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK  \l "_ENREF_25" \o "Nichols, 2012 #14" 25-27] and the surgeon should be able to identify them by sound. ADDIN EN.CITE <EndNote><Cite><Author>Prass</Author><Year>1986</Year><RecNum>20</RecNum><DisplayText>[28]</DisplayText><record><rec-number>20</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">20</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Prass, R. L.</author><author>Luders, H.</author></authors></contributors><titles><title>Acoustic (loudspeaker) facial electromyographic monitoring: Part 1. Evoked electromyographic activity during acoustic neuroma resection</title><secondary-title>Neurosurgery</secondary-title></titles><periodical><full-title>Neurosurgery</full-title></periodical><pages>392-400</pages><volume>19</volume><number>3</number><edition>1986/09/01</edition><keywords><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Electromyography/*methods</keyword><keyword>Evoked Potentials, Auditory</keyword><keyword>Facial Muscles/innervation/*physiology</keyword><keyword>Facial Nerve/physiology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Neuroma, Acoustic/physiopathology/*surgery</keyword><keyword>Neurosurgery/*methods</keyword></keywords><dates><year>1986</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0148-396X (Print)&#xD;0148-396X (Linking)</isbn><accession-num>3762886</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/3762886</url></related-urls></urls><language>eng</language></record></Cite></EndNote>[ HYPERLINK  \l "_ENREF_28" \o "Prass, 1986 #20" 28]  In general, the surgeon should be familiar with two patterns of EMG activity: neurotonic and motor unit discharges. Neurotonic discharges are characterized by irregular, high frequency (50-300 Hz) burst and train EMG. Motor unit discharges are characterized by relatively regular and sustained low-frequency EMG. Of greatest concern is Neurotonic EMG, which is caused by nerve compression, traction or blunt trauma. Motor unit potentials are volitional and can be informative about insufficient patient hypnosis. While the sound of EMG activity may serve to heighten the surgeon�s awareness, not all patterns of EMG activity are cause for concern and attempting to differentiate EMG patterns by sound alone is inadvisable. Also, in the electrically hostile environment of the operating room, one must also be able to detect true neuronal activity and distinguish it from 60-cycle noise and other forms of electrical interference, which should be reduced or eliminated when possible. This underscores the importance of having an experienced neurophysiologist present to interpret the waveforms.
When EMG firing patterns are classified based on waveform morphology, amplitude, frequency and duration, most patterns of EMG activity are benign in terms of predicting postoperative morbidity, and only �A-train� activity is highly predictive of postoperative nerve dysfunction. ADDIN EN.CITE <EndNote><Cite><Author>Romstock</Author><Year>2000</Year><RecNum>98</RecNum><DisplayText>[26]</DisplayText><record><rec-number>98</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">98</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Romstock, J.</author><author>Strauss, C.</author><author>Fahlbusch, R.</author></authors></contributors><auth-address>Department of Neurosurgery, University of Erlangen-Nuremberg, Germany. johann.romstoeck@neurochir.med.uni-erlangen.de</auth-address><titles><title>Continuous electromyography monitoring of motor cranial nerves during cerebellopontine angle surgery</title><secondary-title>J Neurosurg</secondary-title></titles><periodical><full-title>J Neurosurg</full-title></periodical><pages>586-93</pages><volume>93</volume><number>4</number><edition>2000/10/03</edition><keywords><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Cerebellar Diseases/*surgery</keyword><keyword>Cerebellopontine Angle/*surgery</keyword><keyword>Cranial Nerve Diseases/diagnosis/*etiology</keyword><keyword>Cranial Nerves/pathology/*physiology</keyword><keyword>Electromyography</keyword><keyword>Facial Paralysis/etiology/pathology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Monitoring, Intraoperative</keyword><keyword>Motor Neurons/pathology/*physiology</keyword><keyword>Postoperative Complications/diagnosis/prevention &amp; control</keyword><keyword>Predictive Value of Tests</keyword><keyword>Prognosis</keyword></keywords><dates><year>2000</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0022-3085 (Print)&#xD;0022-3085 (Linking)</isbn><accession-num>11014536</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11014536</url></related-urls></urls><electronic-resource-num>10.3171/jns.2000.93.4.0586</electronic-resource-num><language>eng</language></record></Cite></EndNote>[ HYPERLINK  \l "_ENREF_26" \o "Romstock, 2000 #98" 26] A-train activity is a form of neurotonic EMG activity characterized by a sudden onset, irregular, high amplitude (100-200 �V), high frequency (60-210 Hz) discharge that can last for several seconds. Trains lasting longer than 10 seconds have been associated with postoperative deficit; ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK  \l "_ENREF_29" \o "Prell, 2007 #22" 29] however, it is critically important to remain aware that absence of sEMG activity is not necessarily indicative of stable nerve function. Indeed, it has been shown that EMG activity may be absent following serious nerve injury, including sharp dissection. ADDIN EN.CITE <EndNote><Cite><Author>Nelson</Author><Year>1995</Year><RecNum>12</RecNum><DisplayText>[30]</DisplayText><record><rec-number>12</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">12</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Nelson, K. R.</author><author>Vasconez, H. C.</author></authors></contributors><auth-address>Department of Neurology, University of Kentucky Medical Center, Lexington 40536-0084.</auth-address><titles><title>Nerve transection without neurotonic discharges during intraoperative electromyographic monitoring</title><secondary-title>Muscle Nerve</secondary-title></titles><periodical><full-title>Muscle Nerve</full-title></periodical><pages>236-8</pages><volume>18</volume><number>2</number><edition>1995/02/01</edition><keywords><keyword>Aged</keyword><keyword>Biopsy/adverse effects</keyword><keyword>*Electromyography</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Monitoring, Intraoperative/*methods</keyword><keyword>Spinal Nerves/*injuries/physiopathology</keyword></keywords><dates><year>1995</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>0148-639X (Print)&#xD;0148-639X (Linking)</isbn><accession-num>7823985</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/7823985</url></related-urls></urls><electronic-resource-num>10.1002/mus.880180215</electronic-resource-num><language>eng</language></record></Cite></EndNote>[ HYPERLINK  \l "_ENREF_30" \o "Nelson, 1995 #12" 30] Thus, the surgeon must remain aware that free-running sEMG has limited sensitivity to nerve injury. Nevertheless, recording sEMG is particularly important during tissue retraction and tumor dissection, and real-time auditory feedback can serve as a valuable asset to the surgeon when neurotonic EMG activity is recorded. Any observation of neurotonic EMG activity serves as a criterion for alarm and a surgical pause should be initiated immediately to identify and address the problem. 
Stimulus-triggered EMG (tEMG) is recorded at specific points in surgery, as opposed to throughout. A hand-held probe, insulated to the tip, is used to deliver 50�100 �sec, 2.1 Hz constant current stimulation. ADDIN EN.CITE <EndNote><Cite><Author>Prass</Author><Year>1985</Year><RecNum>19</RecNum><DisplayText>[31]</DisplayText><record><rec-number>19</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">19</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Prass, R.</author><author>Luders, H.</author></authors></contributors><titles><title>Constant-current versus constant-voltage stimulation</title><secondary-title>J Neurosurg</secondary-title></titles><periodical><full-title>J Neurosurg</full-title></periodical><pages>622-3</pages><volume>62</volume><number>4</number><edition>1985/04/01</edition><keywords><keyword>Animals</keyword><keyword>Cerebrospinal Fluid Shunts</keyword><keyword>Electric Stimulation/*methods</keyword><keyword>Facial Nerve</keyword><keyword>Humans</keyword><keyword>Neuroma, Acoustic/diagnosis</keyword></keywords><dates><year>1985</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0022-3085 (Print)&#xD;0022-3085 (Linking)</isbn><accession-num>3973737</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/3973737</url></related-urls></urls><language>eng</language></record></Cite></EndNote>[ HYPERLINK  \l "_ENREF_31" \o "Prass, 1985 #19" 31] When a nerve is depolarized, tEMG is recorded in the form of compound muscle action potentials (CMAPs). The recording window is time-locked to the onset of the stimulus, allowing the latency and amplitude of CMAPs to be quantified and compared. 
The tEMG recording epoch can range from 20�50 msec (2�5 msec/division), depending on the expected latency of the CMAP. The window sensitivity is initially set to 50 �V/division, but may be increased to quantify high amplitude CMAPs. Signal gain and band-pass filters are the same as free-running EMG. Whenever tEMG is employed, it is essential to eliminate fluids in the field by applying suction during stimulation. This helps to avoid current shunting�a confound in which a low-resistance path (fluid) directs electrical stimulation away from the desired target. When tEMG is employed, monopolar and bipolar stimulating techniques are available, depending on the needs of the surgeon.
Monopolar stimulation allows current to spread through tissue, utilizing a return electrode placed somewhere on the patient�s body outside of the surgical field, such as the shoulder or sternum. This technique is optimal for probing non-neural tissue (i.e., tumor, muscle and bone) to detect underlying neural elements, as well as rule out their presence. The neurophysiologist is informed about the identity and location of nerves by the threshold, latency and amplitude of the CMAP, as well as the muscle(s) from which it is recorded. Ergo, the closer the neural element is to the locus of stimulation, the lower the threshold required to elicit a CMAP. Additionally, as the locus of stimulation approaches the nerve, the CMAP is likely to exhibit a shorter latency and higher amplitude, and with less spread of excitation to nearby nerves. As a general rule, when a CMAP is evoked with 1.0 mA or less, this is evidence of neural proximity and the surgeon should dissect with caution. More distal cranial nerves may require higher levels of stimulation for depolarization, and the CMAP may exhibit a smaller amplitude and longer latency. Whenever the expected result of stimulation is absence of a response, it is advisable to use a positive control to demonstrate efficacy of stimulation. This can be accomplished either by increasing the current until a CMAP is recorded, or by stimulating an exposed motor/mixed nerve and recording the CMAP. While direct nerve stimulation is always preferred prior to tumor resection, it is often the case that tumors are of sufficient size that they must be partially debulked prior to exposure of neural elements. Monopolar stimulation is advantageous in this situation because ruling out the presence of underlying motor/mixed cranial nerves permits rapid, safe extraction of non-neural tissue. 
Bipolar stimulation limits the spread of current through tissue, because the active and return electrodes are very close together, usually < 3 mm apart. This technique is preferred when the surgeon endeavors to identify a nerve, or determine whether or not a nerve is functional. Identification of a nerve is accomplished with direct electrical stimulation, and the muscle(s) from which the CMAP is recorded help to reveal the identity of the nerve. For example, if an unidentified nerve is stimulated and CMAPs are recorded from the lateral rectus muscle, then the nerve in question is the abducens nerve (CN VI). Basic motor/mixed nerve functionality is assessed by establishing a CMAP threshold, which is defined as the minimum current (mA) required to evoke a CMAP. Beginning at 0.00 mA, the current is carefully increased by 0.01 mA increments until a CMAP is recorded with minimal spread to other nerves/muscles. Nerves should be stimulated frequently during tumor debulking to assess changes in threshold. At the end of the procedure, the nerve should be stimulated on each side of the tumor, proximal and distal to the brainstem, with little expected variation in the CMAP threshold. In the interest of prognostication, a number of methods have been reported for evaluating facial nerve function ADDIN EN.CITE <EndNote><Cite><Author>Minahan</Author><Year>2011</Year><RecNum>96</RecNum><DisplayText>[32]</DisplayText><record><rec-number>96</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">96</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Minahan, R. E.</author><author>Mandir, A. S.</author></authors></contributors><auth-address>Department of Neurology, Intraoperative Neuromonitoring, Georgetown University Hospital, 3800 Reservoir Road NW, Washington DC 20007, USA. rminahan@yahoo.com</auth-address><titles><title>Neurophysiologic intraoperative monitoring of trigeminal and facial nerves</title><secondary-title>J Clin Neurophysiol</secondary-title></titles><periodical><full-title>J Clin Neurophysiol</full-title></periodical><pages>551-65</pages><volume>28</volume><number>6</number><edition>2011/12/08</edition><keywords><keyword>Anesthesia</keyword><keyword>Electromyography</keyword><keyword>Evoked Potentials, Motor/drug effects/*physiology</keyword><keyword>Evoked Potentials, Somatosensory/drug effects/*physiology</keyword><keyword>Facial Nerve/anatomy &amp; histology/drug effects/*physiology</keyword><keyword>Humans</keyword><keyword>Microvascular Decompression Surgery</keyword><keyword>Monitoring, Intraoperative/methods</keyword><keyword>Neural Conduction/physiology</keyword><keyword>Parotid Neoplasms/physiopathology/surgery</keyword><keyword>Trigeminal Nerve/anatomy &amp; histology/drug effects/*physiology</keyword></keywords><dates><year>2011</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>1537-1603 (Electronic)&#xD;0736-0258 (Linking)</isbn><accession-num>22146362</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/22146362</url></related-urls></urls><electronic-resource-num>10.1097/WNP.0b013e318241de1a</electronic-resource-num><language>eng</language></record></Cite></EndNote>[ HYPERLINK  \l "_ENREF_32" \o "Minahan, 2011 #96" 32], but it is unclear if these methods can be generalized to address all motor/mixed cranial nerves.
Electroencephalography 
Electroencephalography (EEG) is used to record the electrical signals produced by neuronal activity in the cerebral cortex. EEG has been utilized to monitor cerebral perfusion in neurovascular procedures for a number of years, and is often the standard of care at many institutions for both extracranial and intracranial vascular monitoring. EEG began to be routinely used in the operating room for vascular monitoring in the 1970s. ADDIN EN.CITE <EndNote><Cite><Author>Sharbrough</Author><Year>1973</Year><RecNum>61</RecNum><DisplayText>[33]</DisplayText><record><rec-number>61</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">61</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Sharbrough, F. W.</author><author>Messick, J. M., Jr.</author><author>Sundt, T. M., Jr.</author></authors></contributors><titles><title>Correlation of continuous electroencephalograms with cerebral blood flow measurements during carotid endarterectomy</title><secondary-title>Stroke</secondary-title></titles><periodical><full-title>Stroke</full-title></periodical><pages>674-83</pages><volume>4</volume><number>4</number><edition>1973/07/01</edition><keywords><keyword>Anesthesia, Inhalation</keyword><keyword>Carbon Dioxide/blood</keyword><keyword>Carotid Arteries/*physiopathology</keyword><keyword>Carotid Artery Diseases/surgery</keyword><keyword>Cerebral Angiography</keyword><keyword>*Cerebrovascular Circulation</keyword><keyword>*Electroencephalography</keyword><keyword>*Endarterectomy</keyword><keyword>Halothane</keyword><keyword>Hemiplegia/etiology</keyword><keyword>Humans</keyword><keyword>Ischemic Attack, Transient/physiopathology</keyword><keyword>Monitoring, Physiologic</keyword><keyword>Oxygen/blood</keyword><keyword>Partial Pressure</keyword><keyword>Postoperative Complications</keyword><keyword>Retinal Artery/physiopathology</keyword><keyword>Xenon</keyword></keywords><dates><year>1973</year><pub-dates><date>Jul-Aug</date></pub-dates></dates><isbn>0039-2499 (Print)&#xD;0039-2499 (Linking)</isbn><accession-num>4723697</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/4723697</url></related-urls></urls><language>eng</language></record></Cite></EndNote>[ HYPERLINK  \l "_ENREF_33" \o "Sharbrough, 1973 #61" 33] While EEG monitoring has gained widespread popularity for vascular monitoring during carotid endarterectomy ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK  \l "_ENREF_34" \o "Ballotta, 2010 #33" 34,  HYPERLINK  \l "_ENREF_35" \o "Deiner, 2010 #54" 35,  HYPERLINK  \l "_ENREF_3" \o "Schloffer, 1907 #73" 3,  HYPERLINK  \l "_ENREF_36" \o "Schneider, 2004 #34" 36,  HYPERLINK  \l "_ENREF_37" \o "Simon, 2012 #38" 37] and cerebral aneurysm surgery ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK  \l "_ENREF_38" \o "Isley, 2009 #39" 38,  HYPERLINK  \l "_ENREF_39" \o "Nuwer, 1993 #40" 39], it is not always routinely used in cavernous sinus or parasellar surgery using the extended endonasal approach. Preoperative clinical imaging helps to show the relationship between the lesion and the vascular anatomy, which is often enveloped or compressed by the tumor. 
A 10 to 16 channel bipolar longitudinal �double-banana� montage (International 10-20 system: Figure 1) can be used to adequately cover gross cerebral cortical perfusion, with enough specificity to help point to different aspects of the anterior, middle, and posterior circulation. This montage results in global cortical coverage of all 4 cerebral lobes across both hemispheres. Increasing the number of channels and leads will help to increase sensitivity and specificity, and can be considered in rare cases where a multimodal approach to neuromonitoring is not feasible. High-pass filtering of <1 Hz and low-pass filtering of 30 Hz is used to record the frequencies seen under general anesthesia. Raw EEG is monitored on all cases, and depending on the neurophysiologist�s preference, quantitative EEG can also be recorded both numerically and as a trend using fast Fourier transformation to facilitate the comparison of EEG activity across different time-points during surgery. It is important to note that, as in all EEG recordings, it is necessary to maintain inter-hemispheric symmetry, with impedances of less than 5 kilohms between homo-topographic leads. Either surface cup electrodes or subdermal needle electrodes can be used. Braiding or twisting the EEG wires will better-enable the amplifier�s common mode rejection to decrease noise in the recordings. 
Although it is rare, iatrogenic vascular injury does occur and can have devastating results. When this occurs, EEG can be used non-invasively to monitor and predict significance in a real-time fashion, without substantial temporal delay. These measures can be used to help determine the need for the patient to be taken to interventional radiology for exploration and treatment, and can also help to show evidence of vasospasm, which otherwise may be undetectable. In the event of vascular rupture, EEG can also be used to assess the amount of pressure applied by packing the surgical site, ensuring that adequate cortical perfusion is maintained. While EEG is useful for measuring adequacy of cortical perfusion, the surgeon must be aware of its limitations. In particular, EEG is not an effective method for monitoring subcortical perfusion or the functional status of eloquent cortex. These structures and functions must be assessed by other measures, and this underscores the importance of multimodality neuromonitoring.
Somatosensory Evoked Potentials
Somatosensory evoked potentials (SSEPs) are one of the most commonly used neuromonitoring IONM modalities, and can be used to assess many different aspects of both the peripheral and central nervous system. Though their use in neurovascular procedures is well documented, very few reports of their use during skull-base procedures exist, ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK  \l "_ENREF_40" \o "Bejjani, 1998 #41" 40,  HYPERLINK  \l "_ENREF_41" \o "Gentili, 1985 #44" 41,  HYPERLINK  \l "_ENREF_19" \o "Tamaki, 2007 #32" 19,  HYPERLINK  \l "_ENREF_9" \o "Thirumala, 2011 #42" 9] and only one of these reports speaks specifically to the transsphenoidal approach. ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK  \l "_ENREF_9" \o "Thirumala, 2011 #42" 9]  SSEPs provide valuable information on the status of both cortical and subcortical function, both in regards to perfusion, as well as long-tract neural integrity. This adds needed information to the clinical picture painted by EEG, which reflects only cortical status, and increases the sensitivity and specificity of the monitoring plan.
SSEPs are recorded from all 4 extremities, with stimulation of bilateral ulnar or median nerves at the wrists, and posterior tibial nerves at the medial ankles. Subdermal needle electrodes are placed approximately 1 cm apart, with the cathode more proximal to the anode. Interleaving square wave pulses of 300 �sec duration are used at a frequency of 4.7 Hz and an intensity of 25-45 mA for the ulnar/median nerves and 35-50 mA for the posterior tibial nerves. Alternate stimulation sites or alternate peripheral nerves can be used when comorbidities preclude recording from these preferred sites. 
Following ulnar or median nerve stimulation, subcortical SSEPs are recorded  over the 2nd cervical vertebra (Cs2), and cortical SSEPs are recorded from the contralateral cerebral hemisphere (C3� or C4�). All recording sites are referenced to Fpz. Following posterior tibial nerve stimulation, subcortical SSEPs are recorded over the 2nd cervical vertebra (Cs2), and cortical SSEPs are recorded from the cerebral vertex (Cz�) or the ipsilateral cerebral hemisphere (C3� or C4�) due to paradoxical lateralization. A trans-cortical montage (P3-P4, P4-P3) can often be used to facilitate signal acquisition if initial cortical amplitudes are low. Band-pass filters of 30-500 Hz are used for subcortical recordings, while 30-300 Hz is typically optimal for cortical recordings.
SSEP signals should be recorded post-induction, but prior to patient positioning. This will help to detect and correct pressure or traction on the brachial plexus or peripheral nervous system. An alarm criterion of a 50% amplitude decrease or a 10% latency shift are traditionally used, both for positioning issues as well as for true iatrogenic changes. While SSEPs provide information regarding the functional status of eloquent cortex and patient positioning, they still have many limitations. These long tract sensory pathways are not fully sensitive to subcortical ischemia, ADDIN EN.CITE <EndNote><Cite><Author>Branston</Author><Year>1984</Year><RecNum>45</RecNum><DisplayText>[42]</DisplayText><record><rec-number>45</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">45</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Branston, N. M.</author><author>Ladds, A.</author><author>Symon, L.</author><author>Wang, A. D.</author></authors></contributors><titles><title>Comparison of the effects of ischaemia on early components of the somatosensory evoked potential in brainstem, thalamus, and cerebral cortex</title><secondary-title>J Cereb Blood Flow Metab</secondary-title></titles><periodical><full-title>J Cereb Blood Flow Metab</full-title></periodical><pages>68-81</pages><volume>4</volume><number>1</number><edition>1984/03/01</edition><keywords><keyword>Animals</keyword><keyword>Arterial Occlusive Diseases/complications/physiopathology</keyword><keyword>Brain Ischemia/etiology/*physiopathology</keyword><keyword>Brain Stem/*physiopathology</keyword><keyword>Cerebral Cortex/*physiopathology</keyword><keyword>Cerebrovascular Circulation</keyword><keyword>*Evoked Potentials, Somatosensory</keyword><keyword>Papio</keyword><keyword>Reaction Time</keyword><keyword>Thalamus/*physiopathology</keyword></keywords><dates><year>1984</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0271-678X (Print)&#xD;0271-678X (Linking)</isbn><accession-num>6693514</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/6693514</url></related-urls></urls><electronic-resource-num>10.1038/jcbfm.1984.9</electronic-resource-num><language>eng</language></record></Cite></EndNote>[ HYPERLINK  \l "_ENREF_42" \o "Branston, 1984 #45" 42] and do not provide any information specific to the motor pathways. In cases where the ischemic penumbra is small or slow to develop, or in cases where only the motor pathways are affected, SSEPs may remain unchanged from baseline parameters, despite evolving hemiparesis. ADDIN EN.CITE <EndNote><Cite><Author>De Vleeschauwer</Author><Year>1988</Year><RecNum>79</RecNum><DisplayText>[43]</DisplayText><record><rec-number>79</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">79</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>De Vleeschauwer, P.</author><author>Horsch, S.</author><author>Matamoros, R.</author></authors></contributors><auth-address>Surgical Department, Akademisches Lehrkrankenhaus, Cologne, West Germany.</auth-address><titles><title>Monitoring of somatosensory evoked potentials in carotid surgery: results, usefulness and limitations of the method</title><secondary-title>Ann Vasc Surg</secondary-title></titles><periodical><full-title>Ann Vasc Surg</full-title></periodical><pages>63-8</pages><volume>2</volume><number>1</number><edition>1988/01/01</edition><keywords><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Aged, 80 and over</keyword><keyword>Brain Ischemia/*diagnosis/physiopathology</keyword><keyword>Carotid Artery, Internal/physiopathology/*surgery</keyword><keyword>Electroencephalography</keyword><keyword>Endarterectomy</keyword><keyword>*Evoked Potentials, Somatosensory</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Monitoring, Physiologic/*methods</keyword><keyword>Prognosis</keyword></keywords><dates><year>1988</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>0890-5096 (Print)&#xD;0890-5096 (Linking)</isbn><accession-num>3228539</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/3228539</url></related-urls></urls><electronic-resource-num>S0890-5096(06)60779-6 [pii]&#xD;10.1016/S0890-5096(06)60779-6</electronic-resource-num><language>eng</language></record></Cite></EndNote>[ HYPERLINK  \l "_ENREF_43" \o "De Vleeschauwer, 1988 #79" 43] These limitations can lead to false negative neurophysiologic testing, and will often need to be supplemented by additional modalities.
Motor Evoked Potentials
Transcranial electrical MEPs (tceMEPs) have played a role in the operating room since multi-pulse stimulation was used to expand the feasibility of the technique, which was developed in the 1980s. ADDIN EN.CITE <EndNote><Cite><Author>Merton</Author><Year>1980</Year><RecNum>46</RecNum><DisplayText>[44]</DisplayText><record><rec-number>46</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">46</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Merton, P. A.</author><author>Morton, H. B.</author></authors></contributors><titles><title>Stimulation of the cerebral cortex in the intact human subject</title><secondary-title>Nature</secondary-title></titles><periodical><full-title>Nature</full-title></periodical><pages>227</pages><volume>285</volume><number>5762</number><edition>1980/05/22</edition><keywords><keyword>Cerebral Cortex/*physiology</keyword><keyword>Electric Stimulation/*instrumentation</keyword><keyword>Electrodes</keyword><keyword>Electroencephalography/instrumentation</keyword><keyword>Humans</keyword><keyword>Visual Perception/physiology</keyword></keywords><dates><year>1980</year><pub-dates><date>May 22</date></pub-dates></dates><isbn>0028-0836 (Print)&#xD;0028-0836 (Linking)</isbn><accession-num>7374773</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/7374773</url></related-urls></urls><language>eng</language></record></Cite></EndNote>[ HYPERLINK  \l "_ENREF_44" \o "Merton, 1980 #46" 44] Given the limitations of both SSEPs and EEG mentioned above, tceMEPs can be used to paint a more comprehensive intraoperative physiologic picture when monitoring cases using the extended endonasal approach, and is often the only means of detecting insult to the long-tract motor pathways. Although the sensitivity and specificity of tceMEPs in detecting functional motor change has been demonstrated for neurovascular procedures, ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK  \l "_ENREF_45" \o "Horiuchi, 2005 #47" 45,  HYPERLINK  \l "_ENREF_46" \o "Neuloh, 2004 #49" 46] literature addressing their efficacy using this particular surgical approach is scarce. 
Either corkscrew or subdermal stimulating leads are placed over C1-C2 or C3-C4 cranially (International 10-20 system: Figure 1) for corticospinal tract activation. Anodal stimulation is used, and this polarity is then reversed for stimulation of the opposite cortical hemisphere. CMAP responses are recorded from the upper and lower extremities. Bipolar subdermal needle electrodes are placed in the extensor carpi radialis, first dorsal interosseous, tibialis anterior, and abductor halluces muscles. This adequately covers long-tract corticospinal function, and has the added benefit of helping to detect and correct positional changes. A multi-pulsed square wave constant voltage stimulus of 50 to 75 �sec duration is used, but voltage and all stimulating parameters are kept purposefully low to help isolate the electrical spread to the contralateral cortical layers, or ipsilateral subcortical pathway. Stimulation parameters that are set too high will bypass the cerebral cortex, and depolarize the pyramidal tracts at subcortical levels, potentially leading to false negative recordings in the event of eloquent cortex motor ischemia. While this is not of concern in spinal procedures, it should always be considered in supratentorial cases. Including contralateral myotomes in the ipsilateral recording trace window helps to identify this limitation. For example, anodal stimulation of the right cerebral hemisphere will produce muscle recordings on the left side of the body. In the recording trace window for the left side of the body, one can include right side myotomes as well. Responses generated from the left myotomes, with absence of responses from the right myotomes, can help to demonstrate focal stimulation that is confined to the right cortical hemisphere. These techniques can help to predict and prevent those rare occasions when other monitoring modalities do not display signal change in the face of evolving hemiparesis.
While electrical activation of the corticospinal tracts has been increasingly utilized across many types of surgical procedures, activation and recording of the corticobulbar tracts has not gained the same popularity. As previously mentioned, lesions in the cavernous sinus or around the clivus will frequently compress or surround the cranial nerves. Although direct cranial nerve stimulation with compound muscle action potential (CMAP) threshold recording is the gold-standard for cranial nerve IONM, it is often the case that large tumors must be partially debulked prior to localization of neural elements. This initial debulking of the tumor can result in iatrogenic injury, prior to the baseline stimulation. Corticobulbar motor evoked potentials (CoMEPs) would allow one to establish a baseline response prior to surgical manipulation, much in the same way that the extremity baselines are established. This would also allow real-time assessment to occur on a more frequent basis, as the surgeon would not have to pause the surgery in order to stimulate with a hand-held probe. The ability to record CoMEPs has been demonstrated in various cranial nerves. ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK  \l "_ENREF_47" \o "Deletis, 2009 #63" 47-50]  Like the tceMEPs for corticospinal activation, it is imperative that the electrical activation is limited to the poly-neuronal corticobulbar tract, and not spread through deeper structures or around the periphery of the scalp and face.  Frequently, there is also a great deal of stimulus artifact present in the responses, which obscure the desired signal due to the short latency of these responses. Dong and colleagues first described the technique to elicit and record these responses. ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK  \l "_ENREF_48" \o "Dong, 2005 #62" 48] Bipolar needle electrodes would be placed in the same muscles used to record EMG activity. Like the tceMEPs for corticospinal activation, a multi-pulsed stimulus would be required to overcome the effects of anesthesia. A response that can be recorded both to single-pulse stimulation would suggest that this is a response generated by activation of the peripheral pathways because a centrally-mediated response can only be recorded to a multi-pulsed stimulus train. Dong and colleagues found that stimulation at C3/C4-Cz (Figure 1) with the anode contralateral to the operative side, and the cathode central, would produce more reliable responses along the corticobulbar pathways, and would also help to eliminate the artifact that is common to these responses. In general, CoMEPs can be very challenging to interpret and do not always correlate well with the postoperative neurological outcome. ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK  \l "_ENREF_51" \o "Morota, 2010 #51" 51,  HYPERLINK  \l "_ENREF_8" \o "Sala, 2007 #50" 8] Due to the trial by trial variability of responses, an undefined alert criteria, and the potential for a high number of false positives and negatives, CoMEPs have not become routine. Further investigation is required before predictive values can be established that allow CoMEPs to be used during skull base endoscopic procedures.
Brainstem Auditory Evoked Potentials
Intraoperative recording of brainstem auditory-evoked potentials (BAEPs) are recorded in surgery to monitor vascular perfusion, as well as functional integrity, of the ascending auditory system, including the vestibulocochlear nerve (CN VIII) and associated brainstem tracts and nuclei. 	
BAEPs are recorded in response to auditory (click) stimulation delivered to the ears through expanding foam earbuds placed in the external auditory canal.  The click consists of a 99 dB (nHL), 100 �sec pulse presented to each ear in alternating fashion at a frequency range of 9.1�17.1 Hz. A referential recording montage is used in which an active recording lead is placed on the earlobe or mastoid (A1/A2), and a reference electrode is placed on the vertex of the head (Cz of the International 10-20 system: Figure 1). The signal is band-pass filtered (100-1500 Hz) and displayed on a computer screen in real time as the response is averaged over many hundreds of trials. Because the BAEP is a far-field response, it is small in amplitude (usually less than 1 �V), but nevertheless robust and repeatable when hearing is intact. 
	The BAEP consists of a waveform with approximately 5 distinct peaks, labeled I-V, which reflect neuronal activity through the ascending auditory pathway. The neural generators for the peaks are I) distal auditory nerve, II) proximal auditory nerve, III) cochlear nucleus, IV) superior olivary complex, and V) lateral lemniscus or inferior colliculus. ADDIN EN.CITE <EndNote><Cite><Author>Legatt</Author><Year>2002</Year><RecNum>11</RecNum><DisplayText>[52]</DisplayText><record><rec-number>11</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">11</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Legatt, A. D.</author></authors></contributors><auth-address>Montefiore Medical Center and the Albert Einstein College of Medicine, Bronx, New York 10467-2490, USA. Legatt@aecom.yu.edu</auth-address><titles><title>Mechanisms of intraoperative brainstem auditory evoked potential changes</title><secondary-title>J Clin Neurophysiol</secondary-title></titles><periodical><full-title>J Clin Neurophysiol</full-title></periodical><pages>396-408</pages><volume>19</volume><number>5</number><edition>2002/12/13</edition><keywords><keyword>Anesthesia</keyword><keyword>Auditory Pathways/physiopathology</keyword><keyword>Brain Stem/physiology</keyword><keyword>Data Interpretation, Statistical</keyword><keyword>Ear/*physiology</keyword><keyword>Electric Stimulation</keyword><keyword>Evoked Potentials, Auditory, Brain Stem/*physiology</keyword><keyword>Humans</keyword><keyword>Hypothermia/physiopathology</keyword><keyword>Mesencephalon/physiopathology</keyword><keyword>*Monitoring, Intraoperative</keyword><keyword>Neuroma, Acoustic/physiopathology/surgery</keyword><keyword>Reference Standards</keyword><keyword>Technology Assessment, Biomedical</keyword><keyword>Time Factors</keyword><keyword>Vestibulocochlear Nerve/physiopathology</keyword><keyword>Vestibulocochlear Nerve Injuries</keyword></keywords><dates><year>2002</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0736-0258 (Print)&#xD;0736-0258 (Linking)</isbn><accession-num>12477985</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12477985</url></related-urls></urls><language>eng</language></record></Cite></EndNote>[ HYPERLINK  \l "_ENREF_52" \o "Legatt, 2002 #11" 52] There are several longer-latency (non-brainstem-generated) peaks that represent higher thalamic and cortical auditory processing, but these peaks are suppressed by anesthetic agents. ADDIN EN.CITE <EndNote><Cite><Author>Legatt</Author><Year>2008</Year><RecNum>71</RecNum><DisplayText>[53]</DisplayText><record><rec-number>71</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">71</key></foreign-keys><ref-type name="Book">6</ref-type><contributors><authors><author>Legatt, A. D.</author></authors><secondary-authors><author>Nuwer, M. R.</author></secondary-authors></contributors><titles><title>BAEPs in surgery</title><secondary-title>Intraoperative Monitoring of Neural Function:Handbook of Clinical Neurophysiology</secondary-title></titles><section>334-349</section><dates><year>2008</year></dates><pub-location>Amsterdam</pub-location><publisher>Elsevier</publisher><isbn>978-0444518248</isbn><urls></urls></record></Cite></EndNote>[ HYPERLINK  \l "_ENREF_53" \o "Legatt, 2008 #71" 53] The technical and pathological mechanisms that may underlie changes in the BAEP are numerous. ADDIN EN.CITE <EndNote><Cite><Author>Legatt</Author><Year>2002</Year><RecNum>11</RecNum><DisplayText>[52]</DisplayText><record><rec-number>11</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">11</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Legatt, A. D.</author></authors></contributors><auth-address>Montefiore Medical Center and the Albert Einstein College of Medicine, Bronx, New York 10467-2490, USA. Legatt@aecom.yu.edu</auth-address><titles><title>Mechanisms of intraoperative brainstem auditory evoked potential changes</title><secondary-title>J Clin Neurophysiol</secondary-title></titles><periodical><full-title>J Clin Neurophysiol</full-title></periodical><pages>396-408</pages><volume>19</volume><number>5</number><edition>2002/12/13</edition><keywords><keyword>Anesthesia</keyword><keyword>Auditory Pathways/physiopathology</keyword><keyword>Brain Stem/physiology</keyword><keyword>Data Interpretation, Statistical</keyword><keyword>Ear/*physiology</keyword><keyword>Electric Stimulation</keyword><keyword>Evoked Potentials, Auditory, Brain Stem/*physiology</keyword><keyword>Humans</keyword><keyword>Hypothermia/physiopathology</keyword><keyword>Mesencephalon/physiopathology</keyword><keyword>*Monitoring, Intraoperative</keyword><keyword>Neuroma, Acoustic/physiopathology/surgery</keyword><keyword>Reference Standards</keyword><keyword>Technology Assessment, Biomedical</keyword><keyword>Time Factors</keyword><keyword>Vestibulocochlear Nerve/physiopathology</keyword><keyword>Vestibulocochlear Nerve Injuries</keyword></keywords><dates><year>2002</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0736-0258 (Print)&#xD;0736-0258 (Linking)</isbn><accession-num>12477985</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12477985</url></related-urls></urls><language>eng</language></record></Cite></EndNote>[ HYPERLINK  \l "_ENREF_52" \o "Legatt, 2002 #11" 52] The petroclival approach places the brainstem at risk for ischemia secondary to vascular compromise (arterial compression, rupture or vasospasm), and BAEPs are sensitive to these changes. Knowledge of the neural generators for the potential can reveal the location and extent of the injury. For example, a major ischemic accident secondary to basilar artery rupture may result in disappearance of waves I-V because perfusion of the cochlea via the internal auditory artery may be compromised. Ischemia of higher brainstem structures may preserve waves I-III, but abolish or delay wave V. When these changes do not resolve during the course of surgery, postoperative deficits are to be expected. ADDIN EN.CITE <EndNote><Cite><Author>Legatt</Author><Year>2002</Year><RecNum>11</RecNum><DisplayText>[52]</DisplayText><record><rec-number>11</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">11</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Legatt, A. D.</author></authors></contributors><auth-address>Montefiore Medical Center and the Albert Einstein College of Medicine, Bronx, New York 10467-2490, USA. Legatt@aecom.yu.edu</auth-address><titles><title>Mechanisms of intraoperative brainstem auditory evoked potential changes</title><secondary-title>J Clin Neurophysiol</secondary-title></titles><periodical><full-title>J Clin Neurophysiol</full-title></periodical><pages>396-408</pages><volume>19</volume><number>5</number><edition>2002/12/13</edition><keywords><keyword>Anesthesia</keyword><keyword>Auditory Pathways/physiopathology</keyword><keyword>Brain Stem/physiology</keyword><keyword>Data Interpretation, Statistical</keyword><keyword>Ear/*physiology</keyword><keyword>Electric Stimulation</keyword><keyword>Evoked Potentials, Auditory, Brain Stem/*physiology</keyword><keyword>Humans</keyword><keyword>Hypothermia/physiopathology</keyword><keyword>Mesencephalon/physiopathology</keyword><keyword>*Monitoring, Intraoperative</keyword><keyword>Neuroma, Acoustic/physiopathology/surgery</keyword><keyword>Reference Standards</keyword><keyword>Technology Assessment, Biomedical</keyword><keyword>Time Factors</keyword><keyword>Vestibulocochlear Nerve/physiopathology</keyword><keyword>Vestibulocochlear Nerve Injuries</keyword></keywords><dates><year>2002</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0736-0258 (Print)&#xD;0736-0258 (Linking)</isbn><accession-num>12477985</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12477985</url></related-urls></urls><language>eng</language></record></Cite></EndNote>[ HYPERLINK  \l "_ENREF_52" \o "Legatt, 2002 #11" 52] A more comprehensive review of mechanisms underlying changes in the AEP is beyond the scope of this paper. 
Visual Evoked Potentials (VEP)
Many lesions arising in the parasellar region result in compression/encasement of the optic nerve or chiasm, often resulting in preoperative clinical visual disturbances. Goggles or contact lenses can deliver a flash stimulus using light emitting diodes (LEDs) to the anesthetized patient, which is then carried through the visual pathways to striate cortex. These signals can be recorded from O1, O2, Oz and Cz with references either to A1/A2 (International 10-20 system). The stimulus frequency and filter settings can vary, but typical stimulation frequency begins at less than 1 flash per second, to 3 flashes per second. Typical filter settings include a bandpass of 1 to 300 Hz, but can be narrowed if stimulation artifact is encountered. This response is usually recorded at its first negative deflection (N70 ms) followed by its first positive deflection (P100 ms). 
It has been demonstrated that decompression of these visual pathways can actually improve postoperative visual neurological testing. ADDIN EN.CITE <EndNote><Cite><Author>Gokalp</Author><Year>1992</Year><RecNum>52</RecNum><DisplayText>[54]</DisplayText><record><rec-number>52</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">52</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gokalp, H. Z.</author><author>Egemen, N.</author><author>Culcuoglu, A.</author><author>Naderi, S.</author><author>Zorlutuna, A.</author></authors></contributors><auth-address>Department of Neurosurgery and Neurology, School of Medicine University of Ankara, Turkey.</auth-address><titles><title>The use of Nd:YAG laser in pituitary surgery and evaluation of visual function by visual evoked potential (VEP)</title><secondary-title>Neurosurg Rev</secondary-title></titles><periodical><full-title>Neurosurg Rev</full-title></periodical><pages>193-7</pages><volume>15</volume><number>3</number><edition>1992/01/01</edition><keywords><keyword>Adenoma/physiopathology/*surgery</keyword><keyword>Adolescent</keyword><keyword>Adult</keyword><keyword>Evoked Potentials, Visual/*physiology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>*Laser Therapy</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Optic Nerve/physiopathology</keyword><keyword>Pituitary Neoplasms/physiopathology/*surgery</keyword><keyword>Postoperative Complications/*physiopathology</keyword><keyword>Reaction Time/physiology</keyword><keyword>Visual Pathways/physiopathology</keyword></keywords><dates><year>1992</year></dates><isbn>0344-5607 (Print)&#xD;0344-5607 (Linking)</isbn><accession-num>1407607</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/1407607</url></related-urls></urls><language>eng</language></record></Cite></EndNote>[ HYPERLINK  \l "_ENREF_54" \o "Gokalp, 1992 #52" 54] On the other hand, it has not been conclusively demonstrated that intraoperative visual evoked potentials (VEPs) can accurately detect and help to prevent iatrogenic injury to the visual pathways. In one study of VEP monitoring during transnasal surgery of 22 patients, intraoperative latency or amplitude change did not correlate with immediate postoperative improvement or deterioration. ADDIN EN.CITE <EndNote><Cite><Author>Chacko</Author><Year>1996</Year><RecNum>53</RecNum><DisplayText>[55]</DisplayText><record><rec-number>53</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">53</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Chacko, A. G.</author><author>Babu, K. S.</author><author>Chandy, M. J.</author></authors></contributors><auth-address>Christian Medical College and Hospital, Vellore, India.</auth-address><titles><title>Value of visual evoked potential monitoring during trans-sphenoidal pituitary surgery</title><secondary-title>Br J Neurosurg</secondary-title></titles><periodical><full-title>Br J Neurosurg</full-title></periodical><pages>275-8</pages><volume>10</volume><number>3</number><edition>1996/06/01</edition><keywords><keyword>Adenoma/physiopathology/*surgery</keyword><keyword>Decompression, Surgical/methods</keyword><keyword>Electroencephalography/*instrumentation</keyword><keyword>Evoked Potentials, Visual/*physiology</keyword><keyword>Humans</keyword><keyword>Monitoring, Intraoperative/*instrumentation</keyword><keyword>Occipital Lobe/physiopathology</keyword><keyword>Pituitary Neoplasms/physiopathology/*surgery</keyword><keyword>Postoperative Complications/*physiopathology</keyword><keyword>Reaction Time/physiology</keyword><keyword>Risk Factors</keyword><keyword>Signal Processing, Computer-Assisted</keyword><keyword>Sphenoid Sinus/surgery</keyword><keyword>Treatment Outcome</keyword><keyword>Vision Disorders/physiopathology/*surgery</keyword><keyword>Visual Acuity/physiology</keyword><keyword>Visual Fields/physiology</keyword><keyword>Visual Pathways/physiopathology/surgery</keyword></keywords><dates><year>1996</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>0268-8697 (Print)&#xD;0268-8697 (Linking)</isbn><accession-num>8799538</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/8799538</url></related-urls></urls><language>eng</language></record></Cite></EndNote>[ HYPERLINK  \l "_ENREF_55" \o "Chacko, 1996 #53" 55] High variability and lack of prognostic value is common with VEPs. Owing to the inconsistency of these recordings, which leads to both false positive and false negative results, VEPs are not routinely monitored during extended endonasal surgeries. 
Anesthesia
Every anesthetic agent administered during surgery will affect neurophysiologic recordings to varying degrees; VEPs are particularly affected, whereas brainstem BAEPs show little fluctuation despite the anesthetic regimen. The success of the monitoring plan relies on cooperation and continuous communication with the anesthesia team. We recommend using total intravenous anesthesia (TIVA; nothing through the mask except oxygen and air)) to facilitate IONM during this surgical approach. TIVA helps to reduce the dose dependent attenuation of signal amplitudes that are usually seen when using inhalational agents, and helps to improve the signal-to-noise ratio, thereby optimizing the monitoring plan. ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK  \l "_ENREF_35" \o "Deiner, 2010 #54" 35,  HYPERLINK  \l "_ENREF_56" \o "DiCindio, 2005 #56" 56-58] As it relates to tceMEPs, the  common agents used in TIVA produce less inhibition at the pyramidal tract synapse on �-motor neurons of the spinal cord. This allows the multi-pulse descending summation to overcome the effects of anesthesia more readily, ultimately producing recordable CMAPs. The patient must also be sufficiently free of pharmacological blockade of the neuromuscular junction to allow both tceMEPs and EMG to be sensitively recorded. Absence of neuromuscular blockade, or sufficient clearance/reversal for reliable monitoring, can be documented by using �train-of-four� (TOF) monitoring, which records muscle twitches in response to stimulation of a peripheral nerve. Using supra-maximal stimulation at 2.0 Hz, TOF can be recorded from the distal extremities to stimulation of the ulnar and posterior tibial nerves, and responses can be recorded from the first dorsal interosseous and abductor halluces muscles, respectively. Short-acting neuromuscular blocking agents can be given to facilitate endotracheal intubation, but are then discontinued for the remainder of the procedure. Currently, there is literature to support partial neuromuscular blockade to help to limit patient movement during surgery where IONM is occurring; however, partial blockade affects different muscle groups to varying degrees, ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK  \l "_ENREF_59" \o "Saitoh, 1996 #99" 59,  HYPERLINK  \l "_ENREF_36" \o "Schneider, 2004 #34" 36] and can be especially variable in a patient with pre-existing neurological dysfunction. ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK  \l "_ENREF_60" \o "Sloan, 2013 #60" 60,  HYPERLINK  \l "_ENREF_58" \o "Sloan, 2002 #55" 58]  
This regimen of anesthesia (TIVA and a full TOF) requires diligent teamwork between the neurophysiologist and the anesthesia team to ensure that there is no patient movement, and that analgesia is adequately controlled. Soft bite blocks will also need to be placed bilaterally between the upper and lower molars or gums to prevent oral trauma with motor tract activation. In doing so, the bite blocks often need to be modified to be small enough to not obstruct the endoscopic entrance to the nares. In cases where a navigation-registration mask is used, insufficient space would be left on the forehead for the anesthesia team to place an �anesthesia consciousness� monitor. The neurophysiologist, having means to assess the patient�s level of sedation and analgesia, can add valuable information about the state of anesthesia, helping to ensure that the patient does not move or have recall during the surgery. 
Discussion
The traditional boundaries of the endonasal-transsphenoidal approach continue to be expanded with advances in instrumentation and microsurgical techniques. Such expansion requires an intimate knowledge of the anatomy encountered along the ventral skull base and clivus. Even with a profound familiarity of the normal structures encountered, anatomical boundaries and relationships may be distorted by the pathology present, creating difficulty with the identification of landmarks. This is particularly true when faced with anomalous vasculature, which confounds the expected anatomy. A multimodal IONM strategy is required to adequately assess the at risk structures. However, because the monitoring modalities used involve stimulating and recording electrical activity, they are dependent upon the integrity of the neural elements being tested. Therefore, a patient presenting with pre-operative neurological deficits confounds the monitoring. Patients with cavernous sinus or suprasellar pathologies will frequently experience preoperative extraocular palsy or visual disturbance. Often, a nerve that is compromised will have an altered threshold, decreased amplitude, increased latency, poor morphology, or no response at all. Marked preoperative clinical neural compromise could create invalid responses, increasing the rates of false positives and negative. CoMEPs through the pathways that innervate the extraocular muscles could help to establish a neural conduction baseline. The methodology for CoMEPs has already been established for corticobulbar pathways, ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK  \l "_ENREF_48" \o "Dong, 2005 #62" 48] although this technique has not been expanded to the nerves that innervate the extraocular muscles. Even if this technique was extrapolated to include these nerves, alarm criteria would need to be established before routine use. 
Electrical stimulation of the nerves to the extraocular muscles is feasible and safe. ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK  \l "_ENREF_61" \o "Alberti, 2001 #1" 61-65]  For management of retroclival lesions, the glossopharyngeal nerve (CN IX), vagus (CN X), spinal accessory (CN XI) and hypoglossal (CN XII) nerves can be safely stimulated. ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK  \l "_ENREF_8" \o "Sala, 2007 #50" 8,  HYPERLINK  \l "_ENREF_66" \o "Schlake, 2001 #23" 66] Adverse consequences include hypotension and bradycardia (CNs IX and X), and muscle and tendon injuries (CN XI). There are no reported adverse consequences of stimulating CN XII. Maintaining low stimulation intensity with a short (25-100 �sec) duration will help to limit stimulation-induced injury. Electrical stimulation of any motor cranial nerve has the added benefit of evaluating the functional integrity of the nerve, especially in the rare event of nerve transection, which does not necessarily result in spontaneous EMG activity.
With the extended endonasal approach, AEPs are primarily used to monitor vascular perfusion of the brainstem when the pathology includes the retroclival structures. Intraoperative AEPs have reliably assessed the integrity and perfusion of both CN VIII and the brainstem during posterior fossa skull base procedures since the late 1970�s. Pathology that approximates the basilar artery or the brainstem necessitates the inclusion of this modality into the monitoring plan, as it helps to complete the total clinical picture in regards to potential sub-cortical ischemia. While the efficacy of AEP�s is well established, the efficacy regarding VEPs is not. As the technology for stimulation devices advances, VEPs may play a larger role in monitoring. The TIVA anesthetic protocol helps stabilize the trial-by-trial variability that is present in the VEP responses. Further research is needed to assess if VEPs can be reliably used as an adjunct to monitor procedures where the visual tracts are affected. 
There is a dearth of literature that addresses IONM during the extended endonasal approach to the skull base. The efficacy of IONM and the modalities chosen by the neurophysiologist to monitor during this approach need to be examined closely, and both case series and case reports are needed to expand the literature base. The monitoring regimen that we present here encompasses a strategy that assesses both cortical and subcortical structures, as well perfusion, and can help to increase the sensitivity and specificity of at risk neural structures during this technically demanding surgical approach. 
Conclusion
Since its introduction by Schloffer in 1907, ADDIN EN.CITE <EndNote><Cite><Author>Schloffer</Author><Year>1907</Year><RecNum>73</RecNum><DisplayText>[3]</DisplayText><record><rec-number>73</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">73</key></foreign-keys><ref-type name="Book">6</ref-type><contributors><authors><author>Schloffer, H.</author></authors><secondary-authors><author>Wien Klin Wochenschr </author></secondary-authors></contributors><titles><title>Erfolreiche Operation eines hypophysentumors auf nasalem wege</title><secondary-title>Wien Klin Wochenschr </secondary-title></titles><volume>20</volume><section>621-624</section><dates><year>1907</year></dates><urls></urls></record></Cite></EndNote>[ HYPERLINK  \l "_ENREF_3" \o "Schloffer, 1907 #73" 3] the utility of the endonasal approach to the anterior cranial base has rapidly expanded. ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK  \l "_ENREF_4" \o "Cavallo, 2005 #77" 4-7] When Jules Hardy introduced the intraoperative microscope in 1967, it revolutionalized transsphenoidal surgery and improved its safety by combining improved magnification and illumination. ADDIN EN.CITE <EndNote><Cite><Author>Hardy</Author><Year>1967</Year><RecNum>67</RecNum><DisplayText>[67]</DisplayText><record><rec-number>67</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">67</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hardy, J.</author></authors></contributors><titles><title>[Surgery of the pituitary gland, using the trans-sphenoidal approach. Comparative study of 2 technical methods]</title><secondary-title>Union Med Can</secondary-title></titles><periodical><full-title>Union Med Can</full-title></periodical><pages>702-12</pages><volume>96</volume><number>6</number><edition>1967/06/01</edition><keywords><keyword>Breast Neoplasms/*therapy</keyword><keyword>Diabetic Retinopathy/*surgery</keyword><keyword>Humans</keyword><keyword>*Hypophysectomy</keyword><keyword>Male</keyword><keyword>Methods</keyword><keyword>Pituitary Diseases/*surgery</keyword><keyword>*Pituitary Irradiation</keyword><keyword>Pituitary Neoplasms/*surgery</keyword><keyword>Prostatic Neoplasms/*therapy</keyword><keyword>Yttrium Isotopes/therapeutic use</keyword></keywords><dates><year>1967</year><pub-dates><date>Jun</date></pub-dates></dates><orig-pub>La chirurgie de l&apos;hypophyse par voie trans-sphenoidale. Etude comparative de deux modalites techniques.</orig-pub><isbn>0041-6959 (Print)&#xD;0041-6959 (Linking)</isbn><accession-num>5630039</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/5630039</url></related-urls></urls><language>fre</language></record></Cite></EndNote>[ HYPERLINK  \l "_ENREF_67" \o "Hardy, 1967 #67" 67] The most recent, and arguably equally significant, advancement in endonasal neurosurgery was the description of the use of the endoscope by Jankowski in 1992. ADDIN EN.CITE <EndNote><Cite><Author>Jankowski</Author><Year>1992</Year><RecNum>68</RecNum><DisplayText>[68]</DisplayText><record><rec-number>68</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">68</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Jankowski, R.</author><author>Auque, J.</author><author>Simon, C.</author><author>Marchal, J. C.</author><author>Hepner, H.</author><author>Wayoff, M.</author></authors></contributors><auth-address>Department of Otorhinolaryngology-Head and Neck Surgery, Central Hospital, University of Nancy, France.</auth-address><titles><title>Endoscopic pituitary tumor surgery</title><secondary-title>Laryngoscope</secondary-title></titles><periodical><full-title>Laryngoscope</full-title></periodical><pages>198-202</pages><volume>102</volume><number>2</number><edition>1992/02/01</edition><keywords><keyword>Adult</keyword><keyword>*Endoscopy</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Methods</keyword><keyword>Middle Aged</keyword><keyword>Pituitary Neoplasms/radiography/*surgery</keyword><keyword>Tomography, X-Ray Computed</keyword></keywords><dates><year>1992</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>0023-852X (Print)&#xD;0023-852X (Linking)</isbn><accession-num>1738293</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/1738293</url></related-urls></urls><electronic-resource-num>10.1288/00005537-199202000-00016</electronic-resource-num><language>eng</language></record></Cite></EndNote>[ HYPERLINK  \l "_ENREF_68" \o "Jankowski, 1992 #68" 68] The subsequent rapid expansion of endoscopic intracranial surgery has permitted access to large areas of the cranial base and its associated pathology. These surgical approaches, however, often require working in close proximity to, and occasionally directly on, the critical neurovascular structures that traverse the cranial base.�
Although the reported rates of vascular injury and cranial nerve deficits following endonasal cranial base surgery are low, these complications can have devastating effects. There is a relatively high potential for postoperative morbidity when addressing cranial base pathology, and all possible efforts must be made to limit that potential. The endoscope itself serves that goal by providing superior illumination and visualization when compared to the operating microscope. Any additional measures that improve the safety of endonasal surgery should be considered, when appropriate.
 IONM has gained widespread acceptance in cranial surgery and has even become standard of care in some settings (e.g., facial nerve monitoring in surgery of the cerebellopontine angle). In this manuscript, we have presented the modalities employed in varying combinations during endoscopic endonasal skull base surgery. Certainly, not all of these techniques are required for every endoscopic endonasal approach.�For example, IONM is unlikely to be beneficial during the resection of standard pituitary adenomas without cavernous sinus invasion. For those lesions that do involve the cavernous sinus and its associated neurovascular structures, or for pathology requiring an extended endonasal approach, an IONM regimen tailored to the specific approach and the at-risk anatomy is utilized (Table 1). In doing so, however, it is necessary to recognize the rationale for each modality as well as its potential limitations. 
References
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2.	Rosen, MR, et al. (2006) A review of the endoscopic approach to the pituitary through the sphenoid sinus. Curr Opin Otolaryngol Head Neck Surg. 14(1): p. 6-13.
3.	Schloffer, H (1907) Erfolreiche Operation eines hypophysentumors auf nasalem wege. Wien Klin Wochenschr ed. W.K. Wochenschr. Vol. 20. 1907.
4.	Cavallo, LM, et al. (2005) Extended endoscopic endonasal approach to the pterygopalatine fossa: anatomical study and clinical considerations. Neurosurg Focus. 19(1): p. E5.
5.	Kassam, A, et al. (2005) Expanded endonasal approach: the rostrocaudal axis. Part I. Crista galli to the sella turcica. Neurosurg Focus. 19(1): p. E3.
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Figure Legend
Figure 1 - International 10-20 Electrode Placement System. F: frontal; T: temporal; O: occipital; P: parietal; A: auricular; C: central








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E.</author></authors></contributors><auth-address>Division of Vascular Surgery, Evanston Hospital and ENH Medical Group, IL 60201, USA.</auth-address><titles><title>Carotid endarterectomy with routine electroencephalography and selective shunting</title><secondary-title>Semin Vasc Surg</secondary-title></titles><periodical><full-title>Semin Vasc Surg</full-title></periodical><pages>230-5</pages><volume>17</volume><number>3</number><edition>2004/09/28</edition><keywords><keyword>Aged</keyword><keyword>Aged, 80 and over</keyword><keyword>Arteriovenous Shunt, Surgical/*methods</keyword><keyword>Carotid Stenosis/mortality/surgery/ultrasonography</keyword><keyword>*Electroencephalography</keyword><keyword>Endarterectomy, Carotid/*adverse effects/methods</keyword><keyword>Female</keyword><keyword>Follow-Up Studies</keyword><keyword>Humans</keyword><keyword>Intraoperative Complications/prevention &amp; control</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Monitoring, Intraoperative/*methods</keyword><keyword>Risk Assessment</keyword><keyword>Sensitivity and Specificity</keyword><keyword>Severity of Illness Index</keyword><keyword>Stroke/*prevention &amp; control</keyword><keyword>Survival Analysis</keyword><keyword>Treatment Outcome</keyword><keyword>Ultrasonography, Doppler</keyword><keyword>Vena Cava Filters</keyword></keywords><dates><year>2004</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0895-7967 (Print)&#xD;0895-7967 (Linking)</isbn><accession-num>15449246</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15449246</url></related-urls></urls><electronic-resource-num>S0895796704000468 [pii]</electronic-resource-num><language>eng</language></record></Cite><Cite><Author>Simon</Author><Year>2012</Year><RecNum>38</RecNum><record><rec-number>38</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">38</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Simon, M. V.</author><author>Chiappa, K. H.</author><author>Kilbride, R. D.</author><author>Rordorf, G. A.</author><author>Cambria, R. P.</author><author>Ogilvy, C. S.</author><author>Kwolek, C. J.</author><author>Lamuraglia, G. M.</author><author>Conrad, M. F.</author><author>Furie, K. L.</author></authors></contributors><auth-address>Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. mvsimon@partners.org</auth-address><titles><title>Predictors of clamp-induced electroencephalographic changes during carotid endarterectomies</title><secondary-title>J Clin Neurophysiol</secondary-title></titles><periodical><full-title>J Clin Neurophysiol</full-title></periodical><pages>462-7</pages><volume>29</volume><number>5</number><edition>2012/10/03</edition><keywords><keyword>Academic Medical Centers</keyword><keyword>Aged</keyword><keyword>Boston</keyword><keyword>Brain Ischemia/*diagnosis/etiology/physiopathology/prevention &amp; control</keyword><keyword>Carotid Stenosis/complications/diagnosis/*surgery</keyword><keyword>Constriction</keyword><keyword>*Electroencephalography</keyword><keyword>Endarterectomy, Carotid/*adverse effects</keyword><keyword>Humans</keyword><keyword>Logistic Models</keyword><keyword>Monitoring, Intraoperative/*methods</keyword><keyword>Multivariate Analysis</keyword><keyword>Odds Ratio</keyword><keyword>Predictive Value of Tests</keyword><keyword>Retrospective Studies</keyword><keyword>Risk Assessment</keyword><keyword>Risk Factors</keyword><keyword>Severity of Illness Index</keyword><keyword>Ultrasonography, Doppler, Duplex</keyword></keywords><dates><year>2012</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>1537-1603 (Electronic)&#xD;0736-0258 (Linking)</isbn><accession-num>23027104</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/23027104</url></related-urls></urls><electronic-resource-num>10.1097/WNP.0b013e31826bde88&#xD;00004691-201210000-00015 [pii]</electronic-resource-num><language>eng</language></record></Cite><Cite><Author>Schneider</Author><Year>2004</Year><RecNum>34</RecNum><record><rec-number>34</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">34</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Schneider, J. R.</author><author>Novak, K. E.</author></authors></contributors><auth-address>Division of Vascular Surgery, Evanston Hospital and ENH Medical Group, IL 60201, USA.</auth-address><titles><title>Carotid endarterectomy with routine electroencephalography and selective shunting</title><secondary-title>Semin Vasc Surg</secondary-title></titles><periodical><full-title>Semin Vasc Surg</full-title></periodical><pages>230-5</pages><volume>17</volume><number>3</number><edition>2004/09/28</edition><keywords><keyword>Aged</keyword><keyword>Aged, 80 and over</keyword><keyword>Arteriovenous Shunt, Surgical/*methods</keyword><keyword>Carotid Stenosis/mortality/surgery/ultrasonography</keyword><keyword>*Electroencephalography</keyword><keyword>Endarterectomy, Carotid/*adverse effects/methods</keyword><keyword>Female</keyword><keyword>Follow-Up Studies</keyword><keyword>Humans</keyword><keyword>Intraoperative Complications/prevention &amp; control</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Monitoring, Intraoperative/*methods</keyword><keyword>Risk Assessment</keyword><keyword>Sensitivity and Specificity</keyword><keyword>Severity of Illness Index</keyword><keyword>Stroke/*prevention &amp; control</keyword><keyword>Survival Analysis</keyword><keyword>Treatment Outcome</keyword><keyword>Ultrasonography, Doppler</keyword><keyword>Vena Cava Filters</keyword></keywords><dates><year>2004</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0895-7967 (Print)&#xD;0895-7967 (Linking)</isbn><accession-num>15449246</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15449246</url></related-urls></urls><electronic-resource-num>S0895796704000468 [pii]</electronic-resource-num><language>eng</language></record></Cite><Cite><Author>Ballotta</Author><Year>2010</Year><RecNum>33</RecNum><record><rec-number>33</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">33</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ballotta, E.</author><author>Saladini, M.</author><author>Gruppo, M.</author><author>Mazzalai, F.</author><author>Da Giau, G.</author><author>Baracchini, C.</author></authors></contributors><auth-address>Vascular Surgery Section, Geriatric Surgery Clinic, Department of Surgical and Gastroenterological Sciences, School of Medicine, University of Padua, Padua, Italy. enzo.ballotta@unipd.it</auth-address><titles><title>Predictors of electroencephalographic changes needing shunting during carotid endarterectomy</title><secondary-title>Ann Vasc Surg</secondary-title></titles><periodical><full-title>Ann Vasc Surg</full-title></periodical><pages>1045-52</pages><volume>24</volume><number>8</number><edition>2010/11/03</edition><keywords><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Aged, 80 and over</keyword><keyword>Brain Ischemia/*diagnosis/etiology/physiopathology/prevention &amp; control</keyword><keyword>Carotid Stenosis/physiopathology/*surgery</keyword><keyword>*Cerebrovascular Circulation</keyword><keyword>Chi-Square Distribution</keyword><keyword>Constriction</keyword><keyword>*Electroencephalography</keyword><keyword>Endarterectomy, Carotid/*adverse effects</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Italy</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Monitoring, Intraoperative/*methods</keyword><keyword>Odds Ratio</keyword><keyword>Predictive Value of Tests</keyword><keyword>Proportional Hazards Models</keyword><keyword>Registries</keyword><keyword>Retrospective Studies</keyword><keyword>Risk Assessment</keyword><keyword>Risk Factors</keyword><keyword>Severity of Illness Index</keyword></keywords><dates><year>2010</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>1615-5947 (Electronic)&#xD;0890-5096 (Linking)</isbn><accession-num>21035696</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/21035696</url></related-urls></urls><electronic-resource-num>10.1016/j.avsg.2010.06.005&#xD;S0890-5096(10)00298-0 [pii]</electronic-resource-num><language>eng</language></record></Cite><Cite><Author>Deiner</Author><Year>2010</Year><RecNum>91</RecNum><record><rec-number>91</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">91</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Deiner, S.</author></authors></contributors><auth-address>Department of Anesthesiology, Mount Sinai Medical Center, New York, NY 10029, USA. Stacie.deiner@mountsinai.org</auth-address><titles><title>Highlights of anesthetic considerations for intraoperative neuromonitoring</title><secondary-title>Semin Cardiothorac Vasc Anesth</secondary-title></titles><periodical><full-title>Semin Cardiothorac Vasc Anesth</full-title></periodical><pages>51-3</pages><volume>14</volume><number>1</number><edition>2010/05/18</edition><keywords><keyword>Anesthetics, Inhalation/*administration &amp; dosage/adverse effects</keyword><keyword>Anesthetics, Intravenous/*administration &amp; dosage/adverse effects</keyword><keyword>Electromyography/methods</keyword><keyword>Evoked Potentials, Motor/drug effects</keyword><keyword>Evoked Potentials, Somatosensory/drug effects</keyword><keyword>Humans</keyword><keyword>Monitoring, Intraoperative/*methods</keyword><keyword>Neurosurgical Procedures/methods</keyword></keywords><dates><year>2010</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1940-5596 (Electronic)&#xD;1089-2532 (Linking)</isbn><accession-num>20472627</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/20472627</url></related-urls></urls><electronic-resource-num>10.1177/1089253210362792&#xD;14/1/51 [pii]</electronic-resource-num><language>eng</language></record></Cite><Cite><Author>Schloffer</Author><Year>1907</Year><RecNum>73</RecNum><record><rec-number>73</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">73</key></foreign-keys><ref-type name="Book">6</ref-type><contributors><authors><author>Schloffer, H.</author></authors><secondary-authors><author>Wien Klin Wochenschr </author></secondary-authors></contributors><titles><title>Erfolreiche Operation eines hypophysentumors auf nasalem wege</title><secondary-title>Wien Klin Wochenschr </secondary-title></titles><volume>20</volume><section>621-624</section><dates><year>1907</year></dates><urls></urls></record></Cite><Cite><Author>Ballotta</Author><Year>2010</Year><RecNum>33</RecNum><record><rec-number>33</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">33</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ballotta, E.</author><author>Saladini, M.</author><author>Gruppo, M.</author><author>Mazzalai, F.</author><author>Da Giau, G.</author><author>Baracchini, C.</author></authors></contributors><auth-address>Vascular Surgery Section, Geriatric Surgery Clinic, Department of Surgical and Gastroenterological Sciences, School of Medicine, University of Padua, Padua, Italy. enzo.ballotta@unipd.it</auth-address><titles><title>Predictors of electroencephalographic changes needing shunting during carotid endarterectomy</title><secondary-title>Ann Vasc Surg</secondary-title></titles><periodical><full-title>Ann Vasc Surg</full-title></periodical><pages>1045-52</pages><volume>24</volume><number>8</number><edition>2010/11/03</edition><keywords><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Aged, 80 and over</keyword><keyword>Brain Ischemia/*diagnosis/etiology/physiopathology/prevention &amp; control</keyword><keyword>Carotid Stenosis/physiopathology/*surgery</keyword><keyword>*Cerebrovascular Circulation</keyword><keyword>Chi-Square Distribution</keyword><keyword>Constriction</keyword><keyword>*Electroencephalography</keyword><keyword>Endarterectomy, Carotid/*adverse effects</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Italy</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Monitoring, Intraoperative/*methods</keyword><keyword>Odds Ratio</keyword><keyword>Predictive Value of Tests</keyword><keyword>Proportional Hazards Models</keyword><keyword>Registries</keyword><keyword>Retrospective Studies</keyword><keyword>Risk Assessment</keyword><keyword>Risk Factors</keyword><keyword>Severity of Illness Index</keyword></keywords><dates><year>2010</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>1615-5947 (Electronic)&#xD;0890-5096 (Linking)</isbn><accession-num>21035696</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/21035696</url></related-urls></urls><electronic-resource-num>10.1016/j.avsg.2010.06.005&#xD;S0890-5096(10)00298-0 [pii]</electronic-resource-num><language>eng</language></record></Cite><Cite><Author>Schneider</Author><Year>2004</Year><RecNum>34</RecNum><record><rec-number>34</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">34</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Schneider, J. R.</author><author>Novak, K. E.</author></authors></contributors><auth-address>Division of Vascular Surgery, Evanston Hospital and ENH Medical Group, IL 60201, USA.</auth-address><titles><title>Carotid endarterectomy with routine electroencephalography and selective shunting</title><secondary-title>Semin Vasc Surg</secondary-title></titles><periodical><full-title>Semin Vasc Surg</full-title></periodical><pages>230-5</pages><volume>17</volume><number>3</number><edition>2004/09/28</edition><keywords><keyword>Aged</keyword><keyword>Aged, 80 and over</keyword><keyword>Arteriovenous Shunt, Surgical/*methods</keyword><keyword>Carotid Stenosis/mortality/surgery/ultrasonography</keyword><keyword>*Electroencephalography</keyword><keyword>Endarterectomy, Carotid/*adverse effects/methods</keyword><keyword>Female</keyword><keyword>Follow-Up Studies</keyword><keyword>Humans</keyword><keyword>Intraoperative Complications/prevention &amp; control</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Monitoring, Intraoperative/*methods</keyword><keyword>Risk Assessment</keyword><keyword>Sensitivity and Specificity</keyword><keyword>Severity of Illness Index</keyword><keyword>Stroke/*prevention &amp; control</keyword><keyword>Survival Analysis</keyword><keyword>Treatment Outcome</keyword><keyword>Ultrasonography, Doppler</keyword><keyword>Vena Cava Filters</keyword></keywords><dates><year>2004</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0895-7967 (Print)&#xD;0895-7967 (Linking)</isbn><accession-num>15449246</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15449246</url></related-urls></urls><electronic-resource-num>S0895796704000468 [pii]</electronic-resource-num><language>eng</language></record></Cite><Cite><Author>Simon</Author><Year>2012</Year><RecNum>38</RecNum><record><rec-number>38</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">38</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Simon, M. 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L.</author></authors></contributors><auth-address>Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. mvsimon@partners.org</auth-address><titles><title>Predictors of clamp-induced electroencephalographic changes during carotid endarterectomies</title><secondary-title>J Clin Neurophysiol</secondary-title></titles><periodical><full-title>J Clin Neurophysiol</full-title></periodical><pages>462-7</pages><volume>29</volume><number>5</number><edition>2012/10/03</edition><keywords><keyword>Academic Medical Centers</keyword><keyword>Aged</keyword><keyword>Boston</keyword><keyword>Brain Ischemia/*diagnosis/etiology/physiopathology/prevention &amp; control</keyword><keyword>Carotid Stenosis/complications/diagnosis/*surgery</keyword><keyword>Constriction</keyword><keyword>*Electroencephalography</keyword><keyword>Endarterectomy, Carotid/*adverse effects</keyword><keyword>Humans</keyword><keyword>Logistic Models</keyword><keyword>Monitoring, Intraoperative/*methods</keyword><keyword>Multivariate Analysis</keyword><keyword>Odds Ratio</keyword><keyword>Predictive Value of Tests</keyword><keyword>Retrospective Studies</keyword><keyword>Risk Assessment</keyword><keyword>Risk Factors</keyword><keyword>Severity of Illness Index</keyword><keyword>Ultrasonography, Doppler, Duplex</keyword></keywords><dates><year>2012</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>1537-1603 (Electronic)&#xD;0736-0258 (Linking)</isbn><accession-num>23027104</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/23027104</url></related-urls></urls><electronic-resource-num>10.1097/WNP.0b013e31826bde88&#xD;00004691-201210000-00015 [pii]</electronic-resource-num><language>eng</language></record></Cite></EndNote>uD���y������K�
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N.</author></authors></contributors><auth-address>Department of Neurological Surgery, Allegheny General Hospital, Pittsburgh, Pennsylvania, USA.</auth-address><titles><title>The predictive value of intraoperative somatosensory evoked potential monitoring: review of 244 procedures</title><secondary-title>Neurosurgery</secondary-title></titles><periodical><full-title>Neurosurgery</full-title></periodical><pages>491-8; discussion 498-500</pages><volume>43</volume><number>3</number><edition>1998/09/11</edition><keywords><keyword>Adolescent</keyword><keyword>Adult</keyword><keyword>Cost-Benefit Analysis</keyword><keyword>*Evoked Potentials, Somatosensory/physiology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Monitoring, Intraoperative/economics/*methods</keyword><keyword>Predictive Value of Tests</keyword><keyword>Skull Base/physiopathology/*surgery</keyword><keyword>Skull Neoplasms/physiopathology/*surgery</keyword></keywords><dates><year>1998</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0148-396X (Print)&#xD;0148-396X (Linking)</isbn><accession-num>9733304</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/9733304</url></related-urls></urls><language>eng</language></record></Cite><Cite><Author>Gentili</Author><Year>1985</Year><RecNum>44</RecNum><record><rec-number>44</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">44</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gentili, F.</author><author>Lougheed, W. M.</author><author>Yamashiro, K.</author><author>Corrado, C.</author></authors></contributors><titles><title>Monitoring of sensory evoked potentials during surgery of skull base tumours</title><secondary-title>Can J Neurol Sci</secondary-title></titles><periodical><full-title>Can J Neurol Sci</full-title></periodical><pages>336-40</pages><volume>12</volume><number>4</number><edition>1985/11/01</edition><keywords><keyword>Adult</keyword><keyword>Auditory Pathways/physiopathology</keyword><keyword>Brain Neoplasms/*surgery</keyword><keyword>Brain Stem/physiopathology</keyword><keyword>*Evoked Potentials</keyword><keyword>Evoked Potentials, Auditory</keyword><keyword>Evoked Potentials, Somatosensory</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Intraoperative Period</keyword><keyword>Middle Aged</keyword><keyword>*Monitoring, Physiologic</keyword><keyword>Postoperative Complications/diagnosis</keyword><keyword>Prognosis</keyword><keyword>Reaction Time</keyword></keywords><dates><year>1985</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>0317-1671 (Print)&#xD;0317-1671 (Linking)</isbn><accession-num>4084873</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/4084873</url></related-urls></urls><language>eng</language></record></Cite><Cite><Author>Thirumala</Author><Year>2011</Year><RecNum>42</RecNum><record><rec-number>42</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">42</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Thirumala, P. 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J.</author><author>Balzer, J.</author></authors></contributors><auth-address>Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. thirumalapd@upmc.edu</auth-address><titles><title>Somatosensory evoked potential monitoring during endoscopic endonasal approach to skull base surgery: analysis of observed changes</title><secondary-title>Neurosurgery</secondary-title></titles><periodical><full-title>Neurosurgery</full-title></periodical><pages>ons64-76; discussion ons76</pages><volume>69</volume><number>1 Suppl Operative</number><edition>2011/03/19</edition><keywords><keyword>Electromyography/methods</keyword><keyword>Evoked Potentials, Somatosensory/*physiology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Monitoring, Intraoperative/*methods</keyword><keyword>*Neuroendoscopy/adverse effects/methods</keyword><keyword>Postoperative Complications/prevention &amp; control</keyword><keyword>Predictive Value of Tests</keyword><keyword>Retrospective Studies</keyword><keyword>Skull Base/*surgery</keyword><keyword>Surgical Procedures, Minimally Invasive/adverse effects/methods</keyword></keywords><dates><year>2011</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>1524-4040 (Electronic)&#xD;0148-396X (Linking)</isbn><accession-num>21415780</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/21415780</url></related-urls></urls><electronic-resource-num>10.1227/NEU.0b013e31821606e4</electronic-resource-num><language>eng</language></record></Cite><Cite><Author>Bejjani</Author><Year>1998</Year><RecNum>41</RecNum><record><rec-number>41</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">41</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bejjani, G. 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H.</author><author>Mintz, A.</author><author>Gardner, P.</author><author>Carrau, R. L.</author></authors></contributors><auth-address>Department of Neurosurgery, Minimally Invasive Neurosurgery Center, Center for Cranial Base Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA. kassamab@upmc.edu</auth-address><titles><title>Expanded endonasal approach: the rostrocaudal axis. Part I. Crista galli to the sella turcica</title><secondary-title>Neurosurg Focus</secondary-title></titles><periodical><full-title>Neurosurg Focus</full-title></periodical><pages>E3</pages><volume>19</volume><number>1</number><edition>2005/08/05</edition><keywords><keyword>Cranial Fossa, Posterior/surgery</keyword><keyword>*Endoscopy</keyword><keyword>Humans</keyword><keyword>Neurosurgical Procedures/*methods</keyword><keyword>Pituitary Neoplasms/surgery</keyword><keyword>Sella Turcica/*surgery</keyword><keyword>Skull Base/*surgery</keyword><keyword>Sphenoid Sinus/*surgery</keyword></keywords><dates><year>2005</year><pub-dates><date>Jul 15</date></pub-dates></dates><isbn>1092-0684 (Electronic)&#xD;1092-0684 (Linking)</isbn><accession-num>16078817</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/16078817</url></related-urls></urls><electronic-resource-num>190103 [pii]</electronic-resource-num><language>eng</language></record></Cite><Cite><Author>Kassam</Author><Year>2005</Year><RecNum>86</RecNum><record><rec-number>86</rec-number><foreign-keys><key app="EN" db-id="a5xsdsv5aafzpberdsqpvapg5ssx2sat929x">86</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kassam, A. B.</author><author>Gardner, P.</author><author>Snyderman, C.</author><author>Mintz, A.</author><author>Carrau, R.</author></authors></contributors><auth-address>Minimally Invasive Endoneurosurgical Center, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA. kassamab@upmc.edu</auth-address><titles><title>Expanded endonasal approach: fully endoscopic, completely transnasal approach to the middle third of the clivus, petrous bone, middle cranial fossa, and infratemporal fossa</title><secondary-title>Neurosurg Focus</secondary-title></titles><periodical><full-title>Neurosurg Focus</full-title></periodical><pages>E6</pages><volume>19</volume><number>1</number><edition>2005/08/05</edition><keywords><keyword>Cavernous Sinus/*surgery</keyword><keyword>Cranial Fossa, Middle/*surgery</keyword><keyword>Cranial Fossa, Posterior/*surgery</keyword><keyword>Craniotomy/methods</keyword><keyword>Endoscopy/*methods</keyword><keyword>Humans</keyword><keyword>Skull Base/*surgery</keyword><keyword>Surgical Procedures, Minimally Invasive/methods</keyword></keywords><dates><year>2005</year><pub-dates><date>Jul 15</date></pub-dates></dates><isbn>1092-0684 (Electronic)&#xD;1092-0684 (Linking)</isbn><accession-num>16078820</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/16078820</url></related-urls></urls><electronic-resource-num>190106 [pii]</electronic-resource-num><language>eng</language></record></Cite></EndNote>sD���y������K�	_ENREF_4uD���y������K�
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