Intraoperative neurophysiologic sensorimotor mapping and monitoring in supratentorial surgery.

INVITED REVIEW

Intraoperative Neurophysiologic Sensorimotor Mapping and Monitoring in Supratentorial Surgery Mirela V. Simon

Summary: It has been shown that aggressive removal of gliomas improves survival and the quality of life in both adults and children. Conversely, there is a strong correlation between incomplete resection of an epileptic focus and poor seizure control outcome in epilepsy surgery. Thus, it is no surprise that maximal resection of supratentorial lesions remains a priority in neurologic surgery. In many circumstances, this is difficult to achieve because of the close proximity of functionally eloquent regions. As a consequence, accurate identification of the latter is imperative to reliably identify safe boundaries for resection and to expand them as much as possible, while preserving neurologic function. Along these lines, preservation of sensorimotor function, with significant impact on postoperative outcome and quality of life, remains essential as achieving maximal resection. Although there is a wide range of methods that could be used for functional sensorimotor mapping, intraoperative neurophysiologic techniques are still considered by many to be the “gold standard.” This article provides a detailed overview of these techniques, their principles, and several alternative methodologies. Although the overview directly reflects the current practice at our institution, it also shows the temporal evolution of the major motor mapping methods, relating them to all significant contributions made over the years by different experts in the field. I have tried to exemplify the relevant points of these techniques by using as many pictures and clinical examples as possible. Key Words: Central sulcus localization, SSEPs phase reversal technique, Cortical motor mapping, Subcortical motor mapping, After discharges. (J Clin Neurophysiol 2013;30: 571–590)

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t has been show that aggressive removal of gliomas has a positive impact on survival rate and the quality of life in both adults and children (Albright et al., 1995; Ammirati et al., 1987; Berger, 1994; Berger, 1996; Guilburd et al., 1989; Nitta and Sato, 1995; Sala et al., 2002; Scerrati et al., 1996; Yang et al., 1999). Similarly, there is a strong correlation between incomplete resection of an epileptic focus and poor seizure control outcome in epilepsy surgery (Bonilha et al., 2004; Kim et al., 2008; Paolicchi et al., 2000). Thus, it is no surprise that maximal resection of supratentorial lesions remains a priority in neurologic surgery. In many circumstances, however, this is difficult to achieve because of the close proximity of functionally eloquent regions (Duffau and Capelle, 2004).

Multimodal Approach I believe one has to embrace a multimodality approach to functional mapping. This is because there is no “perfect” mapping procedure, and each test may add a new element of information and contribute toward achieving a better outcome. From the Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, U.S.A. Address correspondence and reprint requests to Mirela V. Simon, MD, MSc, WACC 739 G, Department of Neurology, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, U.S.A.; e-mail: [email protected]. Copyright Ó 2013 by the American Clinical Neurophysiology Society

ISSN: 0736-0258/13/3006-0571

Visualization of the Anatomy Easily recognizable topographic landmarks, as identified by direct visual inspection in the surgical field or on neuroimaging studies such as magnetic resonance imaging (MRI) studies, have a relatively low interindividual variability and, thus, can be used as surrogates for the location of functionally eloquent cortex (Bitar et al., 2000). However, in case of distorted anatomy, infiltrative pathology and/or neurodevelopmental lesions, the anatomic relationship between these landmarks and functional cortex is often lost, because of displacement, poor demarcation, or plasticity with functional reorganization (see “Dissociation Between Results of Different Neurophysiologic Techniques of Mapping and Monitoring” section). This leads to possible erroneous localization of eloquent regions. In addition, tissue that looks diseased on visual inspection can retain normal function (Ojemann et al., 1996; Schiffbauer et al., 2001; Skirboll et al., 1996). Diffusion tensor imaging (DTI, Kamada et al., 2005, 2007) is a relatively new MRI technique that enables the measurement of the restricted diffusion of water in tissue to produce neural tract images. The principal application remains the mathematical reconstruction of the trajectory of white matter tracts, such as corona radiata and internal capsule, based on the preferential diffusion (anisotropic diffusion) of the water molecules along the length of the axons. However, distortion of this reconstruction with a drop in the signal can be frequently seen in cases of brain lesions characterized by significant vasogenic edema with compression of adjacent regions. In these situations, DTI images may erroneously indicate “destruction” of subcortical fibers in the vicinity of the lesion.

Functional Neuroimaging Functional neuroimaging techniques such as positron emission tomography (Meyer et al., 2003) and functional MRI (Vlieger et al., 2004) can be used preoperatively, with the latter most likely being the most commonly used preoperative cortical functional mapping technique. However, factors such as “distorted” BOLD response in the vicinity of tumor or concomitant hypoperfusion can be responsible for inaccurate mapping. In addition, this technique is task dependent and less specific and, in many instances, does not accurately distinguish between “essential” and “modulatory” regions. In addition, it is restricted to mapping only cortical regions (Holodny et al., 2000; Duffau et al., 2003; Lehericy et al., 2000). Optical intrinsic signal imaging (Pouratian et al., 2002, 2003) is a functional imaging technique still under research, which measures the hemodynamic response to neuronal activity with high spatial and temporal resolution (10 seconds of micron and millisecond, respectively). Light reflecting from the cortical surface is filtered within a narrow wavelength band and captured by a charge-coupled device camera. Change in blood volume and oxygenation produce changes in light reflectance, given the differential absorption of Hbr and HbO2. However, this method does have two shortcomings. First, there is no control over the depth of tissue sampled. Incident photons

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may have undergone any number of scattering events before being collected by the imaging camera. As a result, a relatively thick slab portion of brain tissue, up to several millimeters, may be sampled and averaged across. Second, the majority of studies were performed using red light (.600 nm), producing functional maps that emphasize oxygenation shifts. However, the latter tend to be spatially biased toward venous structures (Frahm et al., 1994). Thus, the resulting functional maps may not accurately portray regions of electrically active cortex. Both these factors may contribute to the observed low specificity of maps as defined by optical intrinsic signal imaging compared with neurophysiologic techniques (Pouratian et al., 2002).

Intraoperative Integration via Functional Neuronavigational Systems It uses coregistered preoperative anatomic and neurofunctional neuroimaging data (Nimsky et al., 2004). However, brain shifts frequently occur intraoperatively, especially once dura is open and during resection, causing loss of precision in appreciating the distances by as much as 15 mm (Nimsky et al., 2005; Reinges et al., 2004).

Preoperative Neurophysiologic Testing Assessing functional connectivity using EEG coherence studies Towle et al. (1998) used EEG spectral power analysis and coherence measurements, as an indirect measure of connectivity and/or “functional likeliness” of different population of neurons, to identify sensorimotor cortex and location of pathological processes. Unfortunately, however, the lack of solid knowledge about the normal distribution of coherence patterns and their relationship to gyral anatomy and/or to certain cortical functions makes accurate interpretation of such studies quite difficult.

Assessing functional encephalography

connectivity

via

magnetic

i. Resting preoperative functional connectivity as assessed by magnetic encephalography (MEG) in the tumoral and peritumoral regions had a 100% negative and 64% positive predictive values for detection of eloquent cortex as identified by intraoperative neurophysiologic technique (i.e., by direct electrical cortical stimulation, Martino et al., 2011). ii. Similarly, based on the principle that damaged brain tissue is disconnected from physiological interactions, Guggisberg and Honma (2008) used MEG to measure the resting state coherence between different areas and peritumoral tissue. The mean imaginary coherence between brain voxels was calculated as an index of functional connectivity, and two maps of functional connectivity were performed: one having as reference the contralateral lesional brain regions; the other similar regions in healthy controls. They found a good association between the level of coherence and postoperative outcome (low coherence indicated a low likelihood of functional damage).

Identification of sensorimotor cortex using MEG i. Cheyne et al. (1991) used the neuromagnetic fields accompanying unilateral and bilateral voluntary movements (i.e., movementrelated magnetic fields) to map sensorimotor cortex. ii. However, Lin et al. (2006) concluded that localization of motor field and movement evoked field using single dipole technique on magnetic source imaging is neither sensitive nor specific enough for preoperative motor mapping. iii. Nagarajan et al. (2008) reliably localized preoperatively the hand motor cortex, using an imaging protocol that used eventrelated desynchronization in beta frequency band obtained by spatial filtering of MEG data. 572

iv. Event-related synchronization of high-frequency gamma oscillations were used by Crone et al. (2006) to map the motor cortex as these oscillations are thought to more closely reflect cortical processing of movement initiation and execution and have an exact temporal relationship with movement onset, carrying a higher specificity to the contralateral movements than event-related desynchronization or event-related synchronization in other frequencies. There is a priori knowledge of what magnitude of event-related synchronization is indicative of cortical processing or more fundamentally, of how much cortical processing is necessary and sufficient for function. However, the neurophysiologic mechanisms specifically responsible for high-gamma event-related synchronization are yet to be elucidated and will likely require additional studies in animals.

Preoperative identification of sensorimotor cortex using evoked potentials This neurophysiologic mapping method is very similar to the one used intraoperatively and includes central sulcus (CS) localization via median somatosensory evoked potential (MSSEPs) phase reversal technique (PRT) and direct electrical stimulation with recording of triggered motor responses in the contralateral hemibody muscles. A detailed description of these methods is further given in the text. There are several disadvantages of the preoperative approach versus the intraoperative approach. i. Preoperatively, the recording of the SSEPs and the cortical stimulation is done via the contacts of a subdural grid electrode, which had been previously implanted. Thus, this method cannot be applied routinely, and it is limited to patients undergoing phase II invasive video-EEG monitoring for epilepsy surgery. ii. Even with sophisticated coregistration techniques available, the reconstructed position of this grid may not be fully accurate. We have had several situations when the grid moved, while implanted, and thus the presumed location of its recording/stimulating electrodes was erroneous. This may lead to tedious and/or false localization of the eloquent cortex. The inability to directly visualize the grid, results in inability to optimize its position. iii. The inability to access the grid may also result in noisy recordings, because of a poor electrode contact with the brain. iv. It is usually done after seizure foci localization, when the patients have poor or no antiepileptic drug coverage (the antiepileptic drugs had been tapered down); thus, it poses an increased risk of stimulation triggered seizures. v. In awake patients, the recording channels for SSEPs and maps are noisier, because of muscle and movement artifact. Advantages of the preoperative neurophysiologic mapping include the following: i. There is less time pressure, as the procedure is done outside the operative room. This gives the neurophysiologist the opportunity to return for more mapping at different occasions or to spend an extended period of time performing mapping. ii. Allows direct communication with the patient. iii. There are no anesthetic effects on the recorded evoked responses.

Intraoperative neurophysiologic mapping In this article, I will present the most commonly used neurophysiologic techniques for mapping the sensorimotor cortex: CS localization via MSSEPs PRT; and direct cortical and subcortical electrical stimulation with recording of the contralateral triggered motor responses, for both motor mapping and monitoring. These methods offer significant advantages: Copyright Ó 2013 by the American Clinical Neurophysiology Society


FIG. 1. The Brodmann areas. Schematic representation of the cytoarchitectonic map of the human cerebral cortex. Sagittal view: lateral hemispheric convexity (A) and medial hemispheric surface (B). Reproduced with permission from Carpenter, 1991. Courtesy of Lippincott Williams & Wilkins. i. They give direct intraoperative feedback to the surgeon. ii. They are not affected by brain shifts that occur after dura opening and during resection. iii. They allow mapping of the corticospinal tract (CST) fibers (Kombos et al., 2009). iv. They allow continuous monitoring of the sensorimotor pathways during the actual resection (Kombos et al., 2001, 2009).

Neurophysiologic–Neuroanatomic Correlation The entire principle of neurophysiologic cortical sensorimotor mapping is based on the anatomy of the pericentral region. Groundbreaking work by the German pathologist Korbinian Brodmann allowed identification of cytoarchitectonically different cortical cerebral hemisphere regions and thus discovery of the Brodmann areas (Fig. 1).

FIG. 2. The sensorimotor homunculus. Reproduced with permission from Carpenter, 1991. Courtesy of Lippincott Williams & Wilkins. Copyright Ó 2013 by the American Clinical Neurophysiology Society

Intraoperative Neurophysiologic Sensorimotor

This in turn raised the question whether these regions have different electrical signature and/or are also different functionally. These theories were confirmed with the discovery of the sensorimotor homunculus (Fig. 2) by Wilder Penfield in the early 1950s (Penfield and Rasmussen, 1950; Penfield and Jasper, 1954). He was able to reliably locate functional eloquent cortex, by using an electrical stimulation paradigm that carries his name, and which has been used consistently since, for both motor and language mapping (Berger et al., 1989). The various regions of the human body are represented somatotopically as shown in Fig. 2, motor regions in the precentral gyrus and homologous sensory regions in the postcentral gyrus. The distorted representation of the body surface, with highest representation for face/tongue, hand, and foot, is thought to echo the higher density of the peripheral innervations and muscle development. The primary somesthetic area (S1) is located in the postcentral gyrus and in the posterior part of the paracentral lobule. This comprises three histologically different strips of cortex: Brodmann areas 3, 1, and 2, from anterior to posterior in a sagittal view (Fig. 1). Area 3 has itself two parts, with 3a situated in the depth of the CS and 3b situated on the posterior wall of the CS. Moving upward to the postcentral gyrus, area 1 represents the top, the crown of this gyrus, whereas area 2 represents the posterior wall of the postcentral gyrus as it reaches toward the postCS. Recording of different cortical components of SSEPs directly from these regions remains at the basis of CS localization (see “Principle” section of “CS Localization” section and Fig. 3). The principal motor cortical regions include the primary motor cortex (PMC), the premotor area, and the supplementary motor area. Brodmann area 4 is commonly designated as the PMC or MI and is located on the anterior wall of CS and on the adjacent portions of the precentral gyrus. The CST, known to transmit impulses for highly skilled volitional movements, arises in large part from this area, which is rich on giant pyramidal Betz cells situated in the ganglionic layer. Virtually, all fibers of CST arise from area 4, area 6, or parietal lobe (Fig. 4). The premotor and supplementary motor areas are situated on the lateral hemispheric convexity, anterior to the PMC and on the medial aspect of the hemisphere, respectively, and both are designated as Brodmann area 6aa (Figs. 1 and 4). The supplementary motor area is also known as MII. Unilateral ablation of the premotor area, without damage to MI and/or MII areas, does not lead to motor deficits or hypertonia. Unlike ablation of MI, which results in permanent motor deficit, unilateral ablation of MII does not produce permanent deficit in initiation of movement or maintaining the posture. However, MII does have an influence on the function of MI and is thought to be involved in programming of skilled motor sequences and in initiation of voluntary movements (Carpernter, 1991). Thus, the temporary motor deficit seen with damage of MII (also known as SMA syndrome) may be, at least partially, related to this function of MII, resulting in reduction of voluntary movements (akinesia), additional to a significant decrease of spontaneous speech. Electrical stimulation of MI will selectively produce motor responses, both electrophysiologically, myogenic motor evoked responses (mMEPs) and clinically (movements) at the lowest stimulus intensity and in specific contralateral myotomes, in direct relationship to the topography of the stimulated regions in the motor homunculus. Identifying the MI threshold is essential in making the distinction between MI and MII, the latter considered having a higher depolarization threshold (Carpenter, 1991). Similarly, the anatomy of the subcortical motor pathways (corona radiata, internal capsule, Fig. 5) is at the basis of the subcortical mapping and clearly highlights why cortical mapping is not sufficient to protect against postoperative motor deficit (see “CST Mapping via Stimulation” section). 573


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FIG. 3. CS region and the cortical SSEPs generators. A, Referential recordings of cortical SSEPs across the CS. Notice the lag of the peak of the precentral positive deflection (ct 2) in comparison with the peak of the postcentral negative deflection (ct 3). B, Diagram representing CS region with the cortical SSEPs dipoles that are at the basis of the SSEPs PRT for CS localization. Notice the location of the pericentral Brodmann areas: 3a, 3b, 1, and 2 as part of the primary somesthetic area (S1); Brodmann area 4 as PMC (aka PMC or MI) vis-a-vis to the location and orientation of these dipoles.

CS LOCALIZATION Principle Because of the close anatomic relationship between locations of CS and PMC, identification of former can be considered the first

FIG. 4. Schematic representation of the motor pathways. Sagittal view of the motor system, showing the cortical origins of the CST. Reprinted with permission from Simon, MV (ed). Intraoperative Neurophysiology: A Comprehensive Guide to Monitoring and Mapping. Copyright Ó 2010 Demos Medical Publishing. 574

step in localizing the latter. In case of normal anatomy, this can be easily achieved by appreciation of the anatomic landmarks on neuroimaging (Bitar et al., 2000). However, pericentral lesions can result in inability to identify topographic landmarks because of infiltrative pathology and/or vasogenic edema, resulting in distortion of the local anatomy and/or “en bloc” displacement. In addition, interindividual variability of the gyral and sulci pattern, whereas not necessarily a frequent occurrence, does exist, and the neuroimaging quality or technique may not allow accurate identification of topographic landmarks. More so, poor calibration of the stealth neuronavigational system can result in erroneous location of CS in the surgical field, even when accurately identified by MRI. Finally, because the only purpose in localizing the CS is for identification of functionally eloquent sensorimotor cortex, presence of functional reorganization/plasticity may result in neurophysiologic–neuroanatomic dissociation, making thus identification of the pericentral anatomy based on visual inspection less helpful. One of the most reliable ways to identify the CS, and indirectly the primary sensorimotor cortex, considered by many the gold standard, remains MSSEPs PRT (Korvenoja et al., 2006; Simon et al., 2010a,b). Electrical stimulation of the median nerve at the wrist is followed at approximately 19 to 20 milliseconds by depolarization of the contralateral (to the stimulation site) postcentral parietal somatosensory cortex, Cpc (i.e., either Cp3 or Cp4 electrode position on 10– 20 International Electrode System). These regions will become more electronegative than the ipsilateral homologous parietal region (Cpi) and than the frontal regions (Fpz, and Fc, i.e., either F3 or F4) and the mastoids (Ac, Ai). Thus, the cortical MSSEPs waveform will reflect this relative electronegativity, showing an upward deflection, N19 (also known as N20), recorded in a Cpc–Cpi, Cpc–Fz, Cpc–Ai channel. However, the absolute latency of the recorded cortical N19/20 will be influenced by several factors, such as: type and depth of anesthesia, presence of somatosensory symptoms, and the patient’s height. At the same latency as the N19, the precentral regions contralateral to the stimulation will become more electropositive than the ipsilateral mastoid. Thus, a downward, positive deflection will be recorded in a Fc–Ai channel. Copyright Ó 2013 by the American Clinical Neurophysiology Society



FIG. 5. Corona radiata: sagittal view of the corona radiata and its relationship to the CS region. The continuity of the motor system explains why exclusive mapping of the cortical motor regions does not preclude the occurrence of postoperative motor deficit. Subcortical mapping and continuous motor monitoring of all the eloquent motor regions are also required. Reproduced with permission from Carpenter, 1991. Courtesy of Lippincott Williams & Wilkins. The MSSEPs PRT is based on recording this dipole, the rapid shift in polarity between the postcentral (negative deflection) and precentral (positive deflection) regions, which occurs at the level of CS. This is possible by simultaneous recordings from the contacts of a subdural strip electrode placed directly on the cortical surface and crossing the CS. However, the precentral regions will acquire the “highest” electropositivity a couple of milliseconds later than the moment when the postcentral regions will become most electronegative. This is because the precentral positivity is partly a consequence of the tangential orientation of the N20/P20 dipole and partly because of a second cortical evoked response (also known as, P22) with the dipole oriented radially, pointing toward the cortex and assumed to have its origin in Brodmann area 4 or even 3a by certain authors (Abbruzzese et al., 1990; Deiber et al., 1986; Desmedt and Ozaki, 1991; Desmedt et al., 1987; Mauguière and Desmedt, 1991; Rossini et al., 1989; Valeriani et al., 1997; Töpper et al., 1993). Thus, the phase reversal created between the upward and the downward peaks point to the CS and, in most situations, does not align perfectly and the positive (downward) peak lags the negative (upward peak) by a couple of milliseconds (Fig. 3). Conversely, because recordings in a bipolar montage register the relative positivity/negativity between two adjacent contacts of the subdural strip, in most situations, we detect more than one phase reversal that is not at the level of CS but rather they will point toward the most electropositive and most electronegative regions (Fig. 6). For this reason, even though we use both reference and bipolar montages, we find the recordings using the former, easier to interpret.

Methodology Stimulation Repetitive pulses at frequencies between 2 and 5 Hz, of 0.1 to 0.3 milliseconds and intensity varying between 10 and 25 mA (the lowest intensity resulting in a robust thumb twitch) are used to stimulate peripherally the median nerve, usually at the wrist (e.g., via Copyright Ó 2013 by the American Clinical Neurophysiology Society

FIG. 6. Phase reversals in cortical SSEPs recordings. The referential montage shows only one phase reversal pointing toward the CS. The bipolar montage two phase reversals, pointing toward hand region on PMC and somatosensory cortex, respectively. two stick-on electrodes; Rochester, Electro-Medical, Inc). To avoid ringing effect, a frequency that is not divisible by 2 or 3 should be used. In awake craniotomies, we first inform the patient what to expect during the stimulation, requesting not to move the stimulated hand/ arm, and we slowly increase the current intensity until a good thumb twitch is obtained (Chiappa, 1997).

Recording We use a sterile eight-contact subdural strip electrode (Ad Tech Manufacturer) placed by the neurosurgeon either subdurally or epidurally, perpendicular to and crossing the presumed location of 575

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desirable; as already mentioned in the stimulation section, the stimulation rate should not be divisible by 2 or 3.

No recorded SSEPs Absence of SSEPs could be because of a technical reason, inappropriate positioning of the recording strip away from the generators (postcentral gyrus for N20, precentral gyrus for P20/ P22) or simply because of destruction/disruption of the somatosensory cortex, as seen in cases of highly infiltrative parietal gliomas. Technical troubleshooting should include checking the adequacy of stimulation (e.g., appropriate placement of the stimulating electrodes, stimulus parameters, and presence of a robust thumb twitch) and of the recordings. Use of anesthetics that can significantly impact generation of cortical SSEPs (i.e., inhalational agents) should be ruled out (see “Inhalational Agents” section; Fig. 18). One of the most common reasons for absence of recordable SSEPs remains placement of the strip away from the somatosensory cortex, mostly because of inaccurate orientation in the surgical field (e. g., poor calibration of the stealth neuronavigational system and distorted anatomy with or without en bloc displacement of the pericentral regions) or because of “blind” placement of the recording strip, sliding it under the dura, and away from the surgical field Fig. 7B. Thus, when all other causes have been ruled out, if there are no reproducible waveforms obtained, it is worthwhile to reposition the strip and restart a new trial.

Interpretation

FIG. 7. Set up for MSSEPs PRT-cortical placement of the recording strip. A, The eight-contact subdural strip electrode (contact 8 by the wire, contact 1 at the tip) is placed across and perpendicular to the CS, at the level of hand region on the hemispheric convexity. B, Placement of the subdural strip electrode away from the surgical field. the CS, at the same “latitude” as the hand area on the contralateral (to the stimulated nerve) hemispheric convexity (Fig. 7A). Each of the contacts of the strip is referenced to either a subdermal needle or a surface stick on electrode placed on the ipsilateral (to the stimulated site) mastoid (Ai). Both bipolar and reference montage recordings are used, as already mentioned (see Principle section of CS Localization section, and Fig. 6).

There are many situations when reproducible SSEPs of same polarity are recorded across all contacts. Whereas such information is better than no SSEPs at all, in most instances fails to be sufficient and still requires further recordings from different strip positions (Fig. 8). Even when guided by topographic landmarks and prior coregistred data, and after multiple repositioning of the recording strip, the surgeon may not find the ideal position for the strip that will allow recording of a phase reversal pointing to the location of CS. More so, a perfect phase reversal recording (Fig. 6) is rather the exception than the rule. Luckily, there are also many times when successful PRT does require neither a phase reversal nor a strip repositioning but instead more selective recording from at least one of the following regions: the somatosensory cortex, PMC, and hopefully across the CS (Figs. 9A and 9B). We have recently identified several factors that slow down the rate at which CS is successfully identified using MSSEPs PRT (Sheth et al., 2013). These include postcentral invasive pathology, perilesional edema causing significant mass effect, and distortion of pericentral anatomy. Conversely, deep total intravenous anesthesia (TIVA) as appreciated by the depth of the burst suppression (BS) pattern and epidural (rather than subdural) recordings do not impact the efficiency of PRT.

Troubleshooting Increased noise Intraoperative recordings are notoriously noisy. Pulsation artifact and electrical interference are probably the two most common reasons. In case of significant pulsation artifact, it is recommended to try repositioning the recording strip and avoid the proximity of cortical vessels. To improve the contact between the recording strip and the cortical surface, we found useful placing soaked sterile gauze on top of the subdural strip. This can also help in case of poor electrode impedances; irrigation of the strip contacts with warm saline, again strip repositioning, or replacing the strip altogether is recommended in case the defective contacts, especially when they are adjacent to the presumed CS (and thus essential for successful results). With regard to the 60-Hz noise, identifying and eliminating the source is always 576

PMC MAPPING VIA STIMULATION Principle After CS localization via SSEPs PRT, reliable identification of the PMC and different parts of the motor homunculus can be made using direct electrical cortical stimulation. The technique is based on early recordings from medulla (Patton and Amassian, 1954) of electrical volleys traveling through the CST (i.e., D waves) after stimulation of the motor cortex. Similarly, the stimulation elicited D waves can be also recorded at the level of spinal cord, whereas muscle motor evoked responses (mMEPs) or compound muscle action potentials are recorded directly from the Copyright Ó 2013 by the American Clinical Neurophysiology Society



FIG. 8. Using recording strip repositioning to optimize results in MMEPs PRT. A, Recording of the N19 potential (arrow) at all contacts (1 through 7) from a strip placed entirely over the postcentral regions (not crossing CS), with contact 1 being the most posterior and contact 7 being the closest to the CS. B, The same strip is rotated 1808 (contact 1 is the most anterior) and slid more anteriorly in an atttempt to cross the CS. The changes in morphology of the waveforms recorded at contacts 1 through 3 indicate that the tip of the strip barely crossed the CS, with contacts 4 and 5 reliably recording the N19 (arrow), thus considered postcentral. C, The strip is pushed further anteriorly; contacts 1 and 2 start showing a definite positivity, indicating location over the precentral regions; contacts 3 and 4 are the closest to the CS; contact 5 records N19 (arrow) and is considered to be the first contact reliably identified as being postcentral. D, The strip is pushed further anteriorly and slightly rotated; contacts 1 through 3 record an electropositive peak (P22) and, thus, are considered to be located precentrally; contacts 5 through 7 record an electronegative peak (N19) and, thus, are considered to be located postcentrally. The CS is located between contacts 3 and 5, likely closest to contact 4. contralateral hemibody muscles. When electrical stimulus is strong enough, clinical movements are also elicited in the corresponding muscles and can be used as “mapping end results.” From all the three electrically triggered responses, the D waves, even though very robust to anesthetics and specific for CST, require placement at the spinal cord level and under fluoroscopic guidance, of an epidural recording electrode. This is an invasive procedure that carries additional risks, such as bleeding, infection, and spinal cord trauma, and thus these types of recordings are not used for supratentorial mapping. During the electrical cortical stimulation, continuous electrocorticogram (ECoG) recording is necessary to detect possible stimulation triggered afterdischarges (ADs) that can pose a safety risk to the patient by both organizing in clinical seizures and causing false positive mapping results (see “ADs and Seizures Triggered by Electrical Stimulation” and “Stimulation” sections).

Methodology Stimulation For mapping, I recommend a monopolar handheld stimulator (e.g., Prass standard monopolar stimulator probe; MedronicXomed, Inc.), connected to the anode and a sterile needle (e.g., disposable subdermal needle, stainless steel, 12 mm length/27 G diameter; Viasys Healthcare), placed by the surgeon in the surgical field, connected to the cathode. The advantage of anodal (over cathodal) stimulation in cortical motor mapping has been well documented (Hern et al., 1962; Ranck, 1975). This relates to a high-frequency anodal stimulation paradigm, also known as the multipulse train technique for stimulation (Neuloh and Schramm, 2002). It consists of applying a train or trains (e.g., 1 Hz) of brief pulses (i.e., 0.5-millisecond pulse width), each train consisting of four to six pulses at high frequency (250–500 Hz). We use constant current stimulation but alternatively, constant voltage stimulation can also be used (Kombos et al., 2000). This stimulation Copyright Ó 2013 by the American Clinical Neurophysiology Society

paradigm is substantially different from low-frequency cathodal stimulation, initially used by Dr. Penfield in 1950s (hence carrying his name, i.e., the Penfield method) and extensively used over the years (e. g., Berger et al., 1989) for both motor and language stimulations (repetitive pulses at 50/60 Hz or 1-millisecond pulse width). One of the main advantages of the high-frequency anodal stimulation versus the Penfield technique is that it is less susceptible to anesthetic effects and allows motor mapping under general anesthesia. Another advantage consists of allowing reliable recordings of the mMEPs (compound muscle action potentialss) triggered at PMC threshold. As previously mentioned, by using electrophysiologic responses of the muscles, rather than motor movements, the mapping is done at lower thresholds, which in turns ensures more specific and possibly safer mapping procedure (Taniguchi et al., 1993). Finally, the stimulus artifact encountered during high-frequency anodal stimulation is substantially reduced (when compared with the Penfield method). Figure 10 shows the two stimulation paradigms, the high-frequency anodal stimulation (also known as multipulse train technique) and the low-frequency cathodal stimulation (also known as Penfield technique). Of note, a bipolar handheld stimulator and contacts of a grid or strip subdural electrodes can also be used (see “Continuous Monitoring of the Motor Pathways” section). For the latter, stimulation can either be bipolar (via adjacent contacts) or monopolar (via two contacts at distance); either high-frequency anodal or low-frequency cathodal stimulation can be used. Either of the two stimulus paradigms described above could be used. A third stimulation paradigm has been described to work best in pediatric population, especially when mapping young children (Jayakar et al., 1992). This paradigm allows modifying both stimulus intensity and the pulse width to reach the depolarization threshold of the PMC before the threshold for triggering seizures. Below, I describe the mapping logistics when using constant current high-frequency anodal stimulation for motor mapping under general anesthesia. 577

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FIG. 9. Successful SSEPs PRT does not necessarily require a phase reversal. A, Referential recordings (reference contralateral mastoid) showing N19 potentials at contacts 5 and 6, localized over the somatosensory cortex. B, Referential recordings showing P22 potentials (arrow) at contact 4, localized over the hand area of PMC. The recordings in A and B were obtained from two different mappings (different patients). In both the cases, the recordings were informative in spite of the lack of clear-cut phase reversal.

The stimulation involves a progressive increase in the stimulus intensity, starting as low as 1 mA, followed by incremental increase the stimulus amplitude (depending on the expected PMC depolarization threshold), up to 25 mA. Thus, being able to predict the threshold (Simon et al., 2010a) helps to increase the speed of this escalation, shortening the time to successful mapping. A cortical area, which stimulated at the lowest stimulus amplitude, triggers reliable, reproducible mMEPs in contralateral hemibody muscles, will be considered part of PMC. All cortical regions that stimulated resulted in mMEPs are further marked by the surgeon. Once the motor strip is identified, multipulse train stimulation can also be used during lesionectomy, for continuous functional monitoring of both the PMC and of the CST, as described in Continuous Monitoring of the Motor Pathways section.

Recording the Motor Responses Either whether the patient is awake or anesthetized, we are using triggered mMEPs as end results of the mapping, as we agree with other authors (Yingling et al., 1999) that electrophysiologic recording should be done regardless of the patient’s state (i.e., awake versus anesthetized). I prefer recording directly the electrical activity triggered rather than observing the movements, for several reasons: (1) the stimulation threshold for mMEPs is smaller than that for 578

clinical movements; this allows more specific identification of different parts of the motor homunculus, with avoidance of current spread; this also decreases the risk of triggering seizures; (2) triggered mMEPs can be more reliably quantified than motor movements; (3) mMEPs allow a more reliable observation of triggered activity in multiple parts of the contralateral hemibody, with the ability to also retrospectively review the results; (4) muscle channels will also allow identification of muscle activity related to stimulation triggered seizures. This can be easily distinguished from the mMEPs (Fig. 11A). The recording electrodes can be either subdermal needless (e.g., XLTEK, disposable 13 mm length, 27 G) or surface stick on electodes (e.g., Rochester; Electro-Medical, disposable conductive solid gel electrodes) placed for recording from orbicularis oris, orbicularis oculi, masseter, trapezius, deltoid, triceps, brachioradialis, abductor policis brevis, abductor digiti minimi, quadriceps, anterior tibialis, and abductor halluces. Of note, recording via subdermal needle electrodes, although still considered a “surface recording,” will allow for a much “cleaner” recording, by reducing the amount of noise, when compared with the recordings via stick on electrodes. If PMC mapping is done to protect it during resective surgery, I would recommend to use two muscles per recording channel, to “sample” as much as possible from the contralateral hemibody (given the limited number of recording channels) and, thus, to Copyright Ó 2013 by the American Clinical Neurophysiology Society



increase the sensitivity of identifying eloquent cortex. If the PMC mapping is done in for “topographic guidance” purposes (see “Topografic Guidance” section), then one could increase the specificity at the expense of sensitivity, by recording only one muscle per channel.

Troubleshooting

FIG. 10. Stimulation paradigms used in motor mapping and monitoring. A, Penfield method (also known as low frequency cathodal stimulation), consisting in repetitive pulses at 60 Hz and 1 millisecond pulse width. B, Multipulse train technique (also known as high frequency anodal stimulation) consisting of trains of several pulses at high frequency (250 to 500 Hz) and 0.5 milliseconds pulse width. Reprinted with permission from Simon, MV (ed). Intraoperative Neurophysiology: A Comprehensive Guide to Monitoring and Mapping. Copyright Ó 2010 Demos Medical Publishing.

Inability to trigger mMEPs, despite high-stimulus amplitude, should prompt detailed technical troubleshooting to ensure that stimulation and recording set up is appropriate. The type and depth of anesthesia should be checked (see “Anesthetic Considerations” section). Mapping of face area can be challenging. This is usually because of the short latency of the mMEPs triggered in face muscles, especially in the presence of significant amount of stimulus artifact in the recording channels. We recommend recording from tongue muscles whenever possible (mapping under general anesthesia) as these mMEPs are usually very reliable and easier to trigger. Muscle recordings during awake craniotomies are notorious for being very noisy (Fig. 12). On these situations, use of subdermal needles (rather than stick on electrodes) for recordings can be advantageous; even though the patient is “awake” after the opening, analgesia is adequate throughout the procedure and necessary (e.g., the patient’s head if fixed in pins) and is enough to keep the patient comfortable. Inability to triggered mMEPs, despite appropriate anesthesia and set up, should always raise the question of location and orientation in the surgical field 6 the possibility of functional reorganization (i.e., we are not stimulating the motor regions, see “Dissociation between results of different neurophysiologic techniques of mapping and monitoring” section).

FIG. 11. Detection of stimulation triggered seizures. A, The hand muscle channel with triggered “stimulus locked” mMEPs and random muscle activity (the top trials), directly related to a clinical motor seizure triggered by electrical stimulation at 11:26:20. Notice that the two types of muscle activities are different morphologically and can be easily distinguished from each other. B, ECoG recordings from the eight-contact subdural strip electrode, initially used MSSEPs PRT, and now connected to the EEG machine. Notice the stimulus artifact and the small amplitude fast frequency buzz building up at contacts 6 and 7 into an electroclinical seizure. Reprinted with permission from Simon, MV (ed). Intraoperative Neurophysiology: A Comprehensive Guide to Monitoring and Mapping. Copyright Ó 2010 Demos Medical Publishing. Copyright Ó 2013 by the American Clinical Neurophysiology Society

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FIG. 12. Noisy muscle recordings during awake craniotomy. Muscle channel recordings for motor mapping during awake craniotomy. Notice the significant noise level present in all channels and especially visible in brachioradialis–triceps and deltoid–trapezius channels (a combination of electrical and muscle artifact). The small arrows point toward random muscle or movement-related artifact. The big arrows point toward the electrically triggered mMEPs, time locked to the stimulation.

Interpretation

A “positive” motor response mMEPs should be reliable and reproducible after repeated stimulations of the same region. In general, responses are polyphasic. However, simplified morphology can be expected, especially if the patient has already motor weakness in that myotome or owing to anesthesia (especially of inhalational agents). With increase in stimulation, one should expect a decrease in mMEPs latency, more complex morphology, and higher averaged amplitude. As the stimulus is increased, a spread to adjacent (but not identified!) regions will lead to responses seen in other myotomes (Fig. 13). For correct “piece-by-piece” identification of the PMC, I recommend finding its threshold. This is important for differentiating between primary and supplementary motor regions as damage of the former will result in permanent postoperative motor deficit, whereas damage of the latter will cause temporary deficit (SMA syndrome). Stimulation of a cortical area not related to primary motor activity, at an amplitude above the PMC threshold, could still result in mMEPs arising from depolarizing the PMC located “at distance” from the stimulated area; thus, falsely localize the motor strip. Stimulation-triggered mMEPs are time locked to the stimulation and, thus, can be differentiated from spontaneous muscle activity, which has a random appearance on repeated stimulations of the same cortical area (Fig. 12). A motor seizure triggered by electrical stimulation may occur at the same threshold as PMC threshold. However, the seizure related motor movements will cause muscle artifact seen in the recording channels, which, as previously specified, can be easily distinguished from the triggered mMEPs; in addition, synchronization between ECoG showing onset of the electrical seizure and MEPs recordings is helpful in differentiating between triggered mMEPs and muscle/ movement artifact related to seizure activity (Fig. 11B). 580

CST MAPPING VIA STIMULATION Principle and Interpretation

As mentioned in “Neurophysiologic–Neuroanatomic Correlation” section, subcortical mapping is essential in many cases, during resection extending beyond the cortical boundary. Using bipolar handheld stimulator (Penfield paradigm), Duffau et al. (2000, 2002) stimulated the resection cavity at different times during surgery (see “Monitoring Patient’s Motor Performance in Awake Craniotomies” section). He was thus able to map proximal corona radiata–fibers arm/face laterally, leg medially (during resection of precentral tumors); distal corona radiata, posterior limb internal capsule, superior part mesencephalic pedunculi (during resection of frontotemporal/insular tumors); and proximal corona radiata and thalamocortical pathways (during resection of parietal tumors). However, his method uses the same stimulus amplitude as that used for cortical mapping. Looking for an “all or none” response at a predetermined stimulus amplitude does not allow appreciation of the distance between the resection cavity and the CST fibers, as the surgeon gets closer to the subcortical pathways. More recently, subcortical stimulation using monopolar handheld stimulation and high-frequency anodal paradigm allows subcortical mapping during general anesthesia and correlation with continuous mMEPs monitoring during resection (see Continuous Monitoring of the Motor Pathways section). Kamada et al. (2009) plotted the stimulus thresholds at which mMEPs were triggered after subcortical stimulation, against the distance between the stimulation site (within the resection cavity) and the CST as appreciated on DTI reconstruction; thus, the authors were able to mathematically predict the CST threshold at 1.8 mA. The first conclusion drawn was that CST threshold is significantly lower than PMC threshold, as it was to be expected during general Copyright Ó 2013 by the American Clinical Neurophysiology Society



CST fibers is more accurate. Their proposed rule of thumb is “1 mm for 1 mA,” meaning that a drop in subcortical stimulation threshold by 1 mA from a previous stimulation should be interpreted as getting closer to the CST fibers by 1 mm. The authors proposed a threshold cutoff of 3 mA, pointing out that mMEPs triggered by subcortical stimulation at lower than 3 mA, correlate well with postoperative motor deficits (sensitivity of 83% and specificity of 95%) and the instability of the mMEPs during continuous monitoring (see “Interpretation” section). A more recent study (Seidel et al., 2013) points out that the latter correlation is not always the rule and recommends both monitoring and subcortical mapping. We fully agree with this approach with the mention that discrepancy between the two (e.g., no mMEPs responses after subcortical stimulation at low intensity in the presence of instability of the monitored mMEPs) may have a valid reason. In short, we are prepared to perform subcortical mapping any time the surgeon desires to do so and especially when instability of mMEPs during monitoring cannot be explained by technical or anesthesia causes. Our surgeons stop resection at a subcortical threshold of 2 mA or less. If mMEPs are unstable but subcortical stimulation fails to trigger responses, other regions of the resection cavity will be carefully sampled.

Methodology For stimulation, we are using a handheld monopolar stimulator and the high-frequency anodal stimulation, as described in the mapping section. The only difference is that, for subcortical stimulation, the stimulator will be connected to the cathode, while the needle in the field will be connected to the anode. As already mentioned, subcortical stimulation can be also performed using a bipolar handheld stimulator and the Penfield technique. For recording, we use the same set up used for the cortical mapping and motor monitoring.

CONTINUOUS MONITORING OF THE MOTOR PATHWAYS Principle

FIG. 13. The effects of current spread. The figure shows the results of current spread because of stimulation at amplitude above the PMC threshold. When stimulating at 6 mA, mMEPs were recorded only in the deltoid–trapezius (delt–trap) channel. However, stimulation of same area at 8 mA caused widespread motor responses (arrow) in hand, brachioradialis–triceps (brach– tri), and anterior tibialis–quadriceps (AT–quad) channels. anesthesia. They also concluded that Wallerian degeneration may result in negative stimulation, whereas presence of a dual cortical layer may lead to increased CST thresholds. Their main results were similar to those of Nossek et al. (2011). The latter predicted an almost linear relationship between the subcortical MEPs thresholds and the distance from the CST. One important improvement of their method is that they corrected for the intraoperative brain shifts, and thus one could consider that their approximation of the distance between stimulation sites and Copyright Ó 2013 by the American Clinical Neurophysiology Society

Identification of the eloquent motor structures (i.e., PMC and CST/corona radiata, internal capsule) via cortical and subcortical mapping, although essential, in many situations is not sufficient for avoiding postoperative motor deficit related to supratentorial surgery. Thus, after mapping, monitoring of their functional integrity can be achieved by continuous stimulation of the PMC at its depolarization threshold, as established during mapping, with continuous recording of the triggered mMEPs from the contralateral hemibody muscles (Fig. 14). This method can be very useful in protecting the CST even in cases when the PMC is not exposed (Fig. 15). Motor monitoring via high-frequency anodal stimulation has been previously described (Kombos et al., 2001).

Methodology Stimulation Via the subdural strip electrode initially used for SSEPs PRT The orientation of this strip can be either perpendicular to (the same with that used for SSEPs PRT) or parallel to the CS (lying on top of the PMC). i. If the strip is perpendicular to the CS, the electrode showing the highest positivity (and thus indicating the location of the hand region) will be connected to the anode, whereas the subdermal needle present in the field can be connected to the cathode 581

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(Fig. 14). A similar set up has also been described by Suess et al. (2006). The stimulation done at PMC threshold should be done continuously, every few seconds or so. This orientation is particularly useful in cases where PMC is not visualized. The disadvantage remains the fact that only hand MEPs can be monitored at the threshold. ii. If the strip is parallel to CS, then more than one contact can be connected to stimulating anodes (with the subdermal needle connected to the cathode); stimulation via these contacts can be interleaved. Each contact will stimulate at PMC threshold a different region of the motor strip; thus, a larger part of the motor homunculus can be monitored. Alternatively, the stimulation can be done via two of the strip contacts; once again, by alternating the polarity of these contacts, stimulation of different parts of the motor homunculus can be achieved (Fig. 15). All the other contacts of the strip that are not used for stimulation can be connected to the EEG machine and used for monitoring for ADs (Fig. 11B). However, if the surgical exposure permits, instead of one strip, two such strips can be used, one for stimulation and the other for recording ADs, as shown in Fig. 15 (Simon et al., 2012). The stimulus parameters are identical to those used for mapping (i.e., high-frequency anodal stimulation or multipulse train technique).

Via an active contact (anode) directly on PMC referenced to the ipsilateral scalp Fpi While using the same high frequency anodal stimulation, this method was described as using constant voltage (Kombos et al., 2000).

2-Recording The recording parameters and the recording set up for both mMEPs and ADs are identical with those used in the mapping.

Interpretation As the stimulation via the strip electrodes at PMC threshold does not cause body movements, it can be done continuously, every few seconds or so. As long as the anesthetic regimen remains stable, the triggered mMEPs should also maintain the amplitudes, morphologies, and latencies. Sudden decrease in their amplitudes, increase in latencies, and simplification of their morphology (e.g., from polyphasic to biphasic) constitute alarm criteria and should prompt the surgeon to stop the resection (Quiñones-Hinojosa et al., 2005; Calancie and Molano, 2008; Kombos et al., 2001). In this situation, communication with the surgical team is essential. Before further action, the position of the stimulating strip electrode needs to be first checked and ensure that it has not changed. This can happen inadvertently, as the resection continues, because of brain shifts, etc. Second, one has to ensure that the anesthetic regimen has not been modified, although the neurophysiologic changes seen with changes in types and doses of anesthetics take longer and are slowly progressive in time (even after bolus administration, it takes minutes rather than seconds for changes to occur). Frequently, one witnesses decrease in mMEPs amplitudes after irrigation of the surgical field with cold water. Once all these causes have been ruled out, ideally, subcortical stimulation should be done in the resection cavity, within the same region where the surgeon was working when changes in the monitored mMEPs occurred. A low threshold (as described in CST Mapping via Stimulation) for

FIG. 14. Continuous motor monitoring “away” from the surgical field. A, Identification of the hand region (electropositivity recorded at contact 5 of the strip). B, Triggered mMEPs in the hand muscle when electrically stimulating the hand area at the PMC threshold, via contact 5 of the subdural strip. C, Continuous monitoring of the hand mMEPs during resection. D, Sagittal view of the lesion pushing forward the precentral cortex. The black bar is a schematic representation of the subdural strip electrode, which was slid under the dura, anterior to the anterior margin of the surgical field. E, Coronal view showing the location of the right hemispheric lesion in relationship to the presumed leg and arm fibers from corona radiata. Although the PMC itself is not exposed and thus is not at risk of damage, the CST fibers are, hence, the need for continuous motor monitoring during resection. 582

Copyright Ó 2013 by the American Clinical Neurophysiology Society



FIG. 15. Continuous motor monitoring using a strip parallel with the CS. A, Right craniotomy exposing the pericentral region. There are two 8-contact subdural strip electrodes placed somewhat parallel to the CS (thick arrow) and pre-CS (thin arrow). The more anterior strip is overlying the PMC and will be used to continuously stimulate this region during resection. The more posterior strip is used exclusively for EcoG monitoring with the purpose of monitoring for ADs. The thin arrow points to sterile needle electrode placed at the margin of the surgical field and connected to the cathode. B, Continuous monitoring of the mMEPs triggered in APB-ADM (contact 6 of the more anterior strip in Fig. 14A, connected to the anode) and brachiorad–triceps (contact 7 anode) channels. Notice the robust responses obtained in these channels throughout resection.

triggering mMEPs in the same muscles as those showing sudden changes in the monitored mMEPs can confirm the validity of the latter. The resection can then be stopped in that direction and the surgeon can redirect it with a different trajectory (Fig. 16). In general, there is a good correlation between instability of the mMEPs during monitoring and a low threshold for triggering mMEPs in the same muscles, via subcortical stimulation (Nossek et al., 2011). However, there are situations when, although mMEPs during monitoring are stable, the mMEPs are triggered at low thresholds via subcortical stimulation in the resection cavity and vice versa (Seidel et al., 2013). First one has to ensure that we are dealing with the same muscle(s) mMEPs. There were instances when, because of the limitations of a small surgical field, although exposing the arm PMC and continuously monitor this region, we could not reach to the leg PMC. Consequently, this was neither identified nor monitored. During resection, although the arm remained stable, stimulation of the resection cavity at low currents triggered mMEPs in the leg muscles (Fig. 16). One also has to keep in mind that the “resolution” in the resection cavity is high, meaning that minimal changes in the position of the handheld monopolar stimulator in the resection cavity may lead to significant changes in the thesholds at which mMEPs are triggered in the corresponding muscles. Thus, if significant changes in the monitored mMEPs are present, and initial subcortical stimulation in the region of interest in the resection cavity does not trigger mMEPs below 3 to 5 mA, I recommend repositioning the handheld stimulator and repeating the stimulation.

Monitoring Patient’s Motor Performance in Awake Craniotomies In awake craniotomies, continuous testing of the awake patients during resection could replace continuous monitoring of the electrically triggered mMEPs. The method has been successfully Copyright Ó 2013 by the American Clinical Neurophysiology Society

used in practice and previously described (Duffau et al., 2003). In a nutshell, identification of the motor cortex is initially done using the Penfield method. During resection, continuous testing is performed (e.g., opening and closing the contralateral hand). When deterioration of the performance is seen, resection is stopped, and subcortical mapping is performed using a handheld bipolar stimulator, as described in “Principle and Interpretation” section. However, I consider this technique as less reliable. This is because deterioration/fluctuation of/in performance can be due not to the resection itself but rather due to fatigability or increase in sedation. In addition, unlike continuous mMEPs monitoring, “continuous” performance from the patient is rather “intermittent”dlarge gaps between two fist closures for example can results in missing the moment when the resection should have been stopped (the onset of these changes). More so, while monitoring the motor movements, it is harder to call changes from a baseline, given the difficulty to rapidly quantify the motor response and the inability to retrospectively “review” or interpret these responses.

SENSORY FUNCTION MAPPING AND MONITORING Primary somatosensory areas in the postcentral regions can be identified during awake craniotomies, by presence or absence of triggered sensory symptoms (usually positive symptoms such as tingling) via electrical cortical stimulation. In addition, both in awake and in anesthetized patients, S1 (Brodmann areas 3, 1, and 2) can be successfully identified by recording SSEPs (the N19/20 component), triggered during stimulation of different peripheral nerves, particularly of the contralateral median nerve (Kumabe et al., 2005). We have already described this method (see CS Localization section). 583


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More so, continuous stimulation of the median nerve allows monitoring of the integrity of the somatosensory cortex and of the thalamocortical pathways during lesionectomy, by appreciating changes from baseline in the triggered N19/20 SSEPs. The alarm criteria consist of sudden changes in the amplitude, morphology, and/or latency of the recorded SSEPs.

SAFETY CONSIDERATIONS ADs and Seizures Triggered by Electrical Stimulation ADs and seizures triggered by stimulation are a safety risk (directly related to clinical seizures) and can also result in erroneous mapping results. Thus, to identify and successfully manage these activities, I recommend EcoG monitoring (Fig. 11B) during the entire period of electrical stimulation (cortical or subcortical). The eightcontact subdural electrode strip (the same as that used for SSEPs PRT) can be successfully used for this purpose, connecting it to the EEG machine. We use both bipolar and referential montages (same reference as that used in SSEPs PRT, i.e., contralateral mastoid). The recording parameters are the same as for a regular EEG recording. Electrocorticograhic (EcoG) recording enables not only identification of the stimulation triggered ADs but also estimation of the degree (if any) of abnormal cortical excitability present at baseline, particularly in patients presenting with seizure activity. This is an

important information, as it is our clinical experience that further electrical stimulation of an already hyperexcitable cortex could trigger more easily such activities. However, this is somewhat different than other authors’ experience (Szelényi et al., 2007); additional antiepileptic drugs given intravenously may be considered in this instance. More so, EcoG by analyzing the depth of the EEG BS pattern, it allows achieving an optimal level of anesthesia, which can lead to a good balance between the motor threshold and the seizure threshold (Simon et al., 2010a,b; Simon, 2011). We find that irrigation with ice-cold Ringer lactate (Sartorius and Berger, 1998) is an efficient method to abort the stimulation triggered ADs or seizures; thus, we recommend that, before the stimulation is initiated, to ensure this is easily available. We have had cases when, especially after intraoperative seizures that were difficult to abort, we elected to continue EEG monitoring throughout the surgery, to rule out nonconvulsive seizures.

Erroneous Interpretation of Sensorimotor Mapping and Monitoring Motor or Sensory Responses Related to Seizures Triggered by Stimulation Any motor or sensory responses “triggered by stimulation” should be discarded as accurate for localizing primary eloquent cortex, in the presence of ADs or seizure activity. Only positive results in the absence of the latter are valid for interpretation.

FIG. 16. Resection of left parietal glioma under neurophysiologic guidance. A, Continuous monitoring of the arm mMEPs during resection of a left parietal glioma (depicted in Fig. 16B). The muscle evoked responses are triggered every several seconds in the right deltoid and hand muscles (the oldest responses at the bottom). Notice the inconsistency of these responses as the resection cavity gets closer to the CST fibers coming from the arm PMC regions (circled). Subsequently, the anterior–lateral resection was stopped. B, Reconstruction of the corona radiata and internal capsule using DTI; integration of the coregistered neuroimaging data using stealth neuronavigational system. Notice the close proximity of the anterior part of the parietal tumor to the CST fibers, with distortion of the corona radiata. C, Stable mMEPs in the deltoid muscles triggered during continuous monitoring. However, notice the high amplitude mMEPs triggered in AH muscle (and to a lesser extend in AT and quad muscles), by subcortical stimulation at 2 mA of the anteriomedial wall of the resection cavity. This prompted the surgeon to stop resection in the anterior– medial direction. 584



Dissociation Between Results of Different Neurophysiologic Techniques of Mapping and Monitoring It is well known that brain lesions induce functional reshaping of both motor homunculus and language networks (Branco et al.,

FIG. 16.


2003; Duffau et al., 2005). This reorganization happens preoperatively more often with slow growing gliomas and as a result of cortical injury early in life (e.g., neurodevelopmental disorders such as cortical dysplasias). However, acute reorganization of functional map can occur

Continued.


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during resection itself owing to locoregional hyperexcitability, with unmasking of redundant motor and somatosensory sites (Duffau, 2001; Duffau and Capelle, 2001). Compensatory functional reorganization can also occur later, in the postsurgical recovery period, because of contralateral hemispheric homologous participation (Kamada et al., 2004; Krainik et al., 2004). Duffau et al. (2000) also describes the possibility of a “redistribution of functions” within a larger perirolandic network. We have come across cases that support the latter theory Fig. 17. This is more so supported by the very cytoarchitectonic anatomy, with fibers of the CST arising not only from Brodmann area 4 but also from area 6 and areas 3, 1, and 2 (Fig. 4). Precisely, because of this plasticity, relying exclusively on topographic landmarks as surrogates for localization of eloquent cortex can be risky as it is using SSEPs PRT as the sole technique for sensorimotor mapping.

cortical excitability, delay axonal transmission in the CST fibers, and decrease the synaptic transmission at the level of the spinal alpha motor neuron (Burke et al., 2000; Haghighi, 1998; Hentschke et al., 2005; Hicks et al., 1992; Loughnan et al., 1989; Osawa et al., 1994; Zentner et al., 1992). Thus, generation of reliable mMEPs triggered by direct cortical stimulation is negatively impacted by these agents, and their use should be avoided. Because the most prominent mechanism of action of these agents is at the cortical level, mMEPs obtained by subcortical stimulation (of the CST fibers) may be less affected. Nevertheless, because of their multiple sites of action, I recommend avoidance of inhalational agents during both cortical and subcortical stimulations.

Total Intravenous Anesthesia ANESTHETIC CONSIDERATIONS Inhalational Agents Inhalational agents such as nitrous oxide and halogenated agents have a significant negative impact on generation of SSEPs and MEPs, especially when used together (Simon, 2010; Simon et al., 2010b).

Somatosensory Evoked Potentials The use of inhalational agents may significantly distort the morphology of the thalamocortical responses and hinder detection of a phase reversal (Fig. 18). However, their impact may be even more significant, leading to total annihilation of identifiable waveforms. Thus, during SSEPs PRT, their use should be limited as much as possible, especially in symptomatic patients.

Muscle Motor Evoked Responses Inhalational anesthetics such as halogenated agents act on the motor pathways at different level within neuroaxis: they decrease

Total intravenous anesthesia (TIVA) (e.g., propofol and remifentanyl) is the anesthetic regimen of choice for both SSEPs and mMEPs recordings in motor mapping. Although TIVA is the preferred anesthetic regimen for sensorimotor mapping, caution needs to be taken to avoid a deep level of anesthesia (especially after administration of intravenous boluses of propofol or after a high propofol infusion rate), which can translate into a deep EEG BS pattern (Kortelainen et al., 2007). It is our clinical experience that this will result in significantly high motor thresholds (Simon, 2010; Simon et al., 2010a,b). In general, if the length of EEG flats in the BS pattern exceeds on average 2 to 3 seconds, we inform and ask the anesthesiologist to decrease the propofol infusion rate.

Dexmedetomidine We agree with other authors (Mahmoud et al., 2007) that dexmedetomidine can negatively impact the generation of mMEPs and, thus, should be avoided during motor mapping via electrical stimulation. FIG. 17. Functional reorganization of the pericentral region. A, The pericentral region exposed during a right craniotomy for resection of a low-grade glioma. An eightcontact subdural strip electrode is placed directly on the cortical surface, oriented with contact 8 as most anterior, for localization of the CS via MSSEPs PRT. The surgeon is stimulating the cortex using a handheld monopolar stimulator; hand mMEPs are triggered at the lowest current intensity (PMC threshold) when stimulating the region as shown. B, Recording N19 median SSEPs at contacts 2 through 5 with the most representative at contact 5 (reference montage, reference electrode placed on the contralateral, i.e., left, mastoid). This places contact 5 postcentrally and identifies the sulcus before it as CS. C, The primary hand and leg areas as identified by cortical stimulation and their topographic relationship to the CS; the surgeon is pointing to the leg area with the monopolar stimulator. As noticed, the identified areas are situated posterior to the CS.

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Special Situations: Combined Neurophysiologic Motor and Seizure Foci Mapping A special situation is encountered in epilepsy surgery cases, when both neurophysiologic mapping of the seizure foci and functional mapping are required. Although the former benefits from an anesthetic regimen without propofol (we encourage the use of dexmedetomidine or inhalational agents), we prefer TIVA for the latter. This is because a BS pattern will hinder identification of epileptiform and epileptic activity, while inhalational agents will significantly affect SSEPs and MEPs generation, as mentioned above. Thus, the order in which these two types of mapping will be performed is important and should be discussed in advance with the anesthesiologist and the surgeon. If the EcoG is performed first, from the neurophysiologic perspective, the transition from inhalational agents to TIVA is lengthier than when performed the other way around; this means that the effects of inhalational agents can linger for as much as 30 to 40 minutes, from the minute the gases where turned off and when propofol has already been started; in our experience, this will lead to a relatively deep BS pattern to begin with.

Advantages and Disadvantages of Awake Craniotomies Advantages Keeping the patient awake during the mapping has its own advantages. First, direct communication with the patient and ability to follow the neurological examination and patient’s symptoms,


potentially triggered by stimulation or provoked by resection, can be of great value, especially when the neurophysiologic testing leads to equivocal results. This is particularly of value during somatosensory mapping, when the patient can experience sensory symptoms. In addition, during awake mapping, the depolarization threshold of the eloquent cortex is lower, and the neurophysiologic evoked responses are free from anesthetic effects.

Disadvantages Conversely, patients kept awake during craniotomy can become oversedated and hypoventilate. This may lead to hypercapnia induced brain swelling. Because the patient is not intubated, efficient and prompt control of the latter, by increasing the lung ventilation, is not possible. This can become worrisome, particularly in cases where there is significant brain swelling and mass effect. When the mapping threshold is lower, so is the threshold for electrically triggered seizures. More so, if a generalized tonic–clonic seizure occurs, the lack of airway protection increases the risk of aspiration and makes drug management (benzos, propofol etc) problematic, especially when higher doses are necessary to stop the seizure activity. While performing motor mapping in awake or anesthetized patients, our practice is also to set up recordings for mMEPs. As already mentioned, in awake patients, there is a significant decrease in the signal-to-noise ratio (Fig. 13), when compared with the anesthetized patients, mostly because of the presence of spontaneous muscle activity and occasional voluntary body movements. Last but not least, not all patients tolerate awake procedures, which can be uncomfortable and difficult to tolerate.

FIG. 18. The impact of halogenated agents on MSSEPs PRT. A, Attempt to record cortical SSEPs via an eight-contact strip electrode, 5 minutes after isoflurane was turned off. No reliable SSEPs and/or phase reversal were seen. B, High amplitude, reliable cortical SSEPs, and a definite phase reversal were recorded 40 minutes later, during TIVA and from the same strip position as that used in Fig. 18A. Copyright Ó 2013 by the American Clinical Neurophysiology Society

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For all these reasons, we prefer to perform motor mapping under general anesthesia. More details on this topic are presented elsewhere (Simon et al., 2010b).

CLINICAL APPLICATIONS Neurophysiologic techniques can be successfully applied in supratentorial surgery with several goals.

Protection Protection of functionally vital nervous structures, such as motor and language regions, is undoubtedly the most important role. Table 1 gives the types of surgical procedures that could directly benefit from applying neurophysiologic methods and some specifics for that type of procedure.

Topografic Guidance For Pain Management Neurophysiologic cortical motor mapping has a distinct role in guiding the epidural electrode placement in neuropathic pain (Lefaucheur and de Andrade, 2009; Holsheimer et al., 2007; Manola et al., 2005, 2007). The principle of such pain management relies on the fact that electrical stimulation of the motor cortex corresponding to the contralateral hemibody pain territory will have an analgesic

TABLE 1.

Glioma resection

Metastatic lesions resection Epilepsy surgery

AVM/vascular malformations resection

Temporal lobectomy

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For Diagnostic Purposes in Epilepsy Patients undergoing phase II invasive video EEG monitoring for epilepsy surgery will need implantation of the subdural grid and strip electrodes, with precise placement precisely over the presumed location of the epileptogenic foci. In addition, in cases when these foci are in close proximity to the eloquent cortical regions, it is important that the implanted hardware covers these areas as well, with the purpose of preoperative neurophysiologic mapping of motor regions. Thus, intraoperative neurophysiologic mapping of both seizure foci (via EcOG) and eloquent motor cortex can be very helpful in guiding the placement of this hardware.

Specifics of Intraoperative Neurophysiologic Mapping and Monitoring During Different Supratentorial Surgeries

Type of Procedure

Redo surgery

effect. The latter is due by activation via cathodal stimulation of the horizontal fibers in the superficial cortical layers. Thus, it is very important to detect with precision the motor homunculus area representing the part of the contralateral hemibody where the pain is located. For example, in cases of intractable facial pain (e.g., trigeminal neuralgia), it is important to identify with precision the face area. The contact of the epidural strip providing the highest MEPs amplitudes in the pain territory (e.g., masseter MEPs), also known as the best anode, will coincide with the contact providing the best analgesic effect when selected for chronic electrical stimulation (the best cathode). For such cases, when we need an increased specificity of the mapping procedure, I would recommend the use of one muscle per channel recording.

Specifics (1) Slow-growing gliomas are more likely to present with reorganization and plasticity, thus unexpected localization of motor cortex (neuroanatomic–neurophysiologic dissociation) (2) Highly infiltrative tumors and peritumoral edema in close proximity to eloquent regions may lead to higher mapping thresholds (3) Increased mass effect may lead to distorted pericentral anatomy and, thus, increased difficulty in successful mapping (1) Usually pathology is well circumscribed and thus less frequently associated with neurophysiologic–neuroanatomic dissociation (2) Melanomas may pose additional challenge as far as placement of subdural strip and grids, because of increased risk of bleeding (1) Frequently, there is need for both mapping of seizure focus and for functional mapping. During craniotomies under general anesthesia, this presents additional challenge related to the transition from one anesthetic regimen to anther. This is necessary because seizure focus mapping requires avoidance of a burst suppression pattern, and thus inhalational agents are preferred over TIVA. However, sensorimotor mapping is best performed under the latter, whereas inhalational agents can significantly affect the reliability of the results (2) Increased risk for stimulation triggered seizures (3) In case of neurodevelopmental lesions, increased reorganization and plasticity, leading to unexpected location of PMC (1) Cortical mapping is essential for identification of PMC, which will be continuously stimulated at its threshold, during resection; this is important to prevent false negative results resulting from stimulation at unnecessary high stimulus amplitudes, with current spread and stimulation of the CST distal to the resection site (and not proximal to it) (2) Changes during MEPs monitoring can occur at different stages: (a) Dissection: The procedure needs to be halted until the recovery of EPs. If the mechanism is mechanical vasospasm, irrigation with papaverine will help recovery. If the mechanism is traction and kinking of the minor vessels, then readjustment of the retractors will help (b) Temporary clipping: This is sometimes necessary, especially during dissection/exposure; increase in systemic blood pressure, speeding up the procedure, and release of clipping as soon as possible (c) Inadvertent arterial occlusion: Neurophysiologic monitoring techniques are superior to Doppler sonography for occlusion of the small vessels. Occurrence of such changes should prompt to immediate inspection of the surgical field (3) Stable EPs are reassuring during both temporary and permanent clipping and may allow more extensive dissection and exposure (1) Continuous monitoring via SSEPs/MEPs allows assessment of the integrity of internal capsule and adequate vascular supply during traction on the perisylvian regions. EP changes will prompt readjustment of the retractor, to avoid postoperative temporary or permanent deficit (1) Particularly challenging mapping, because of increased likelihood of subdural adhesionsdexpect: (i) lengthy exposure; (ii) difficulty in placing the subdural strip for recording in SSEPs PRT and for electrical stimulation for continuous motor monitoring (2) Expect reorganization of the eloquent cortex



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Intraoperative monitoring of motor-evoked potentials for supratentorial tumor surgery.

Practice patterns for intraoperative neurophysiologic monitoring.

Does intraoperative neurophysiologic monitoring matter in noncomplex spine surgeries?

Intraoperative functional mapping and monitoring during glioma surgery.

SEP Montage Variability Comparison during Intraoperative Neurophysiologic Monitoring.

Surgeon-driven neurophysiologic monitoring in a spinal surgery population.

Functional preoperative and intraoperative mapping and monitoring: increasing safety and efficacy in glioma surgery.

Augmentation of motor evoked potentials using multi-train transcranial electrical stimulation in intraoperative neurophysiologic monitoring during spinal surgery.

Train-of-four test in intraoperative neurophysiologic monitoring: differences between hand and foot train-of-four.

Intraoperative neurophysiological monitoring in spinal surgery.

Intraoperative neural monitoring in thyroid cancer surgery.

Can intraoperative neurophysiologic monitoring during cervical spine decompression predict post-operative segmental C5 palsy?

Neurophysiologic monitoring during surgery of peripheral and cranial nerves, and in selective dorsal rhizotomy.

Sensorimotor mapping of the human cerebellum during pineal region surgery.

Editorial: Intraoperative neurophysiological monitoring and spinal deformity surgery.

Comparative effectiveness analyses of intraoperative neurophysiological monitoring in spinal surgery.

Intraoperative monitoring of facial nerve function in cerebellopontine angle surgery.

Intraoperative Neurophysiologic Monitoring for Prediction of Postoperative Neurological Improvement in a Child With Chiari Type I Malformation.

Intraoperative nerve monitoring during total shoulder arthroplasty surgery.

Overview of Intraoperative Neurophysiological Monitoring During Spine Surgery.

Intraoperative electroencephalographic monitoring during carotid surgery with routine shunting.

Supratentorial Intraparenchymal Haemorrhages during Spine Surgery.

Intraoperative Monitoring and Mapping of the Functional Integrity of the Brainstem.

Intraoperative electrophysiological monitoring in children.