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Multimodal functional mapping of sensorimotor cortex prior to resection of an epileptogenic perirolandic lesion
Epilepsy & Behavior Epilepsy & Behavior 5 (2004) 407–410 www.elsevier.com/locate/yebeh
Case Report
Multimodal functional mapping of sensorimotor cortex prior to resection of an epileptogenic perirolandic lesion Heidi E. Kirsch,a,* Jehuda P. Sepkuty,b and Nathan E. Croneb a
UCSF Epilepsy Center, Department of Neurology, University of California San Francisco School of Medicine, San Francisco, CA, USA b Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA Received 15 January 2004; revised 5 February 2004; accepted 10 February 2004 Available online 19 March 2004
Abstract The effects of chronic epileptogenic lesions on functional anatomy are under debate. Our recent experience during mapping and resection of a lesion in sensorimotor cortex supports the idea that epileptogenic lesions may prompt development of alternate cortical motor representations. Multimodal mapping may uncover alternate areas of functionality that make surgery feasible even when conventional neuroanatomy suggests otherwise. Newer methods such as electrocorticographic spectral analysis may complement traditional electrical cortical stimulation mapping. Ó 2004 Elsevier Inc. All rights reserved. Keywords: Functional mapping; Epilepsy surgery; Electrocorticography; Electrocorticographic spectral analysis; Cortical plasticity; Motor cortex
1. Introduction Evidence from electrical cortical stimulation (ECS) mapping suggests that sensorimotor topography may vary widely [1,2]. In addition, chronic cortical lesions may lead to reorganization of functional anatomy, as demonstrated in primates and in humans [for a review, see 3]. This reorganization presumably occurs by compensatory cortical synaptic reorganization like that observed after experimental manipulation of afferent pathways in animals. With slow-growing lesions of sensorimotor cortex, intraoperative ECS has been used to guide excision to spare function. In some cases, multiple representations for the upper extremity have been identified that were not apparent with ECS before resection, but were demonstrated immediately afterward, suggesting that alternate cortical representations were available [e.g., 4]. Before resection near essential cortical regions, identification of alternate cortical representations might mitigate postoperative deficits.
* Corresponding author. Fax: 1-415-252-2837. E-mail address: [email protected] (H.E. Kirsch).
1525-5050/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2004.02.001
This principle is illustrated by a patient with intractable epilepsy from a chronic perirolandic lesion. Prolonged EEG monitoring showed ictal onset in sensorimotor cortex, complicating surgical planning. Ictal electrocorticographic (ECoG) recordings located the epileptogenic zone in sensorimotor regions identified through extraoperative ECS mapping. However, functional mapping with multiple complementary methods revealed additional surrounding cortical regions that had similar motor function. This allowed us to postulate that alternate cortical representations might minimize the risk of postlesionectomy deficits.
2. Case Our subject was an 18-year-old right handed man with multiple cavernous angiomas (Fig. 1) and intractable simple partial seizures of the right arm, onset at C1/C3/ CP3 scalp electrodes. He also had rare complex partial seizures without lateralizing features (presumably from another source). He underwent implantation of subdural electrodes (platinum–iridium; 2.3-mm-diameter exposed surface; 1-cm center-to-center spacing; Ad-Tech, Racine, WI, USA) to better define his seizure focus (Fig. 2).
408
Case Report / Epilepsy & Behavior 5 (2004) 407–410
stant-current electrical stimulation (biphasic square waves, 300-ls pulse width, 50 Hz, 10–15 mA, 5-s duration) was delivered by a Grass S12 stimulator (Grass Instruments, Quincy, MA, USA) between pairs of adjacent electrodes (bipolar ECS) and between individual electrodes and distant, uninvolved reference electrodes (unipolar ECS). A standard battery of motor tasks were performed during ECS (for a description of the battery, see, e.g., [1]). Signs of functional interference were recorded on videotape and visually interpreted by clinical observers; interference was termed ‘‘positive’’ if stimulation evoked movement and ‘‘negative’’ if it slowed or arrested movement [7]. 2.3. ECoG somatosensory evoked potentials
Fig. 1. T1 axial magnetic resonance image of patientÕs brain; note multiple cavernous angiomas, including the ictal source (white arrow) in the left rolandic region.
A Grass S11 stimulator delivered 300-ms constantcurrent pulses to the right median nerve at motor threshold through wrist surface electrodes (rate ¼ 4.7 Hz, N ¼ 2000) [1]. Signals were averaged over trials with respect to stimulation; N1 (20-ms) and P1 (24-ms) waveforms were used to estimate central sulcus location, and a single moving dipole was modeled using Curry software (Compumedics Neuroscan, El Paso, TX, UAS).
2.1. Neuroimaging 2.4. ECoG spectral analysis (ESA) Preimplantation three-dimensional volumetric MRI was coregistered with postimplantation CT using Curry software (Neurosoft, El Paso, TX, USA) to verify electrode position on cortex; this corresponded to intraoperative digital photography (Fig. 2). Preoperative functional MRI (fMRI) was performed during right-hand complex finger tapping as described by Moo et al. [5]. 2.2. Electrical cortical stimulation mapping ECS mapping was performed according to routine clinical procedures described elsewhere [e.g., 6,7]. Con-
Electrocorticograms were digitally recorded (1000-Hz sampling) during self-paced button press (subject pressed at approximately 10-s intervals without counting). Event-related augmentation of power in an 80–100 Hz ‘‘high gamma’’ band was used to index cortical activation. This index has been validated for visual–motor tasks [8], word production tasks [9], and the task used here [10]. Gamma power augmentation was quantified by digital bandpass (80–100 Hz) filtering and squaring of the ECoG signal, followed by segmentation (100-ms epochs with 50% overlap) and averaging of the resulting
Fig. 2. Intraoperative photographs before and after subdural electrode implantation and after lesion resection. Electrodes are overlying the left central region (arrows point to anatomic central sulcus) and are numbered following indicated sequence. The orientation of the photographs is such that the patientÕs nose is to the viewerÕs upper right, and the top of the patientÕs head is to the viewerÕs lower right.
Case Report / Epilepsy & Behavior 5 (2004) 407–410
power values across trials (N ¼ 50); statistical analyses identified electrodes where gamma band power in poststimulus epochs and prestimulus (baseline) epochs differed significantly (for a description of the analytical method, see [11]). The patientÕs typical simple partial seizures at the right wrist and elbow, with variable involvement of fingers and shoulder, were recorded. Ictal subdural electrocorticography demonstrated onset from cortex overlying an angioma on the anterior lip of a left frontoparietal sulcus. Preoperative fMRI showed that right complex finger tapping activated cortex immediately posterior to the lesion (Fig. 3). ECS of the epileptogenic zone caused right finger, hand, and proximal arm movements (i.e., ‘‘positive interference’’). However, ECS of cortical tissue in a zone surrounding the lesion in all directions and extending up to as far as 3 cm posterior to the lesion and 2 cm inferior to the lesion also caused finger, hand, and proximal arm movements. Stimulation of electrodes 1 cm anterior and 1 cm anterosuperior to the lesion interfered with finger, hand, and proximal arm movements reliably (i.e., ‘‘neg-
409
ative interference’’), but stimulation at some of these electrodes also elicited clonic movements of the face, eyelids, and mouth (i.e., both positive and negative interference). Phase reversal of N1 and P1 of median SEPs (via ECoG) occurred 0.5 cm posterior to the lesion, and calculated equivalent dipoles for these potentials localized to the same spots. ESA high gamma augmentation during self-paced button press occurred maximally in electrodes inferior and posterior to the angioma. The epileptogenic lesion and the overlying cortex were resected. Postoperatively, the patient had mild proximal weakness of the right arm, confined to shoulder shrug, but fine finger movements were unchanged from baseline. Subtle signs of distal pyramidal weakness, such as reduced fluidity of fine finger movements and finger extensor weakness, were absent, as were pronator drift and orbit signs. A week later, strength and dexterity had returned fully to baseline. Six months later, he was free of simple partial seizures, though he continued to have rare complex partial seizures.
3. Discussion
Fig. 3. Cortical surface rendering of preoperative MRI, with subdural electrodes from postoperative CT scan superimposed. As in Fig. 2, electrodes are numbered starting from the upper right hand corner of the array; electrodes 8 and 64 are indicated. Yellow lightning bolts indicate the region of seizure onset. The purple shading indicates the approximate surface projection of the underlying angioma. The light blue shading indicates the approximate region of fMRI activation. The black arrow indicates the anatomic central sulcus, as in Fig. 2. Electrode color indicates the results of ECS mapping. For simplicity, only unipolar right upper extremity results are shown (reference electrode is 8 or 64). Red¼ evoked movement (‘‘positive response’’), green ¼ no deficit with ECS. Slowed or arrested movement (‘‘negative response’’) is not shown here, as it overlapped red regions extensively. Stimulation at the yellow electrode was followed by an evoked seizure in the right hand. Small yellow dots indicate evoked clonic movements in the right upper extremity with bipolar stimulation between adjacent electrode pairs. The blue line indicates the border of the right median SEP phase reversal. Magenta circles indicate regions of maximal 80- to 100-Hz augmentation during a self-paced button press with the right thumb; the size of the circle corresponds to the degree of augmentation seen at a given electrode.
Because the subjectÕs seizure focus was associated with a lesion in the motor strip, detailed motor mapping was necessary to assess the risks of resection. We found a hand motor representation larger than expected by anatomic landmarks alone. This suggested that cortical reorganization had taken place, perhaps due to chronic hemorrhage and/or epileptogenic activity associated with the lesion. ECS mapping in our subject showed multiple areas of similar motor representation; given the expansion and apparent redundancy of hand and finger sensorimotor regions, it was difficult to know which areas might adequately preserve hand motor function if others were resected. The mechanism for the apparent expansion of motor representation is unknown. Duffau posits that there are, in normal individuals as well as those with chronic lesions, multiple redundant circuits for the same motor function that exist within motor cortex [4,12], as well as in somatosensory and language cortex [13]. These redundant cortical representations are latent and capable of being acutely ‘‘unmasked’’ after resection of motor cortex. Another possibility is that chronic epileptiform activity suppressed the normal function of cortex overlying the lesion, and that neighboring regions took over its function. Such changes in the topography of sensorimotor function in the presence of ongoing epileptiform activity without changes in the underlying structural lesion were reported by Lado et al. [14] in a case of serial cortical stimulation mapping with an interval of several years. In our subject, this possibility could not be confirmed. Although cortical stimulation mapping showed multiple areas of similar motor representation, it was difficult to
410
Case Report / Epilepsy & Behavior 5 (2004) 407–410
know which areas might adequately preserve hand motor function if others were resected. In addition, there was no consistent difference in the motor interference produced by ECS between cortex overlying the lesion and neighboring cortex. We were fortunate, however, to have other types of data relying on different mechanisms. Two nonlesional mapping methods, functional MRI and ESA, indicated that regions within ECS-defined cortical hand area specifically activated with voluntary hand movement tasks and did not overlap with the epileptogenic region. These smaller regions were spared during surgical resection in hopes of providing seizure freedom without motor deficit. Although we did not map motor function after our subjectÕs resection, the lack of significant postoperative motor deficit suggests that spared regions were sufficient for hand function. Proximal weakness was confined to shoulder shrug, which recovered acutely as is typical postoperatively for such deficits, perhaps due to bihemispheric representation for such regions. This case demonstrates the potential benefits of using complementary functional mapping methods. Although the effective current density during ECS is circumscribed [15], it may have unforeseen transsynaptic effects on functionally connected cortex. fMRI provides a noninvasive, but indirect, measure of cortical activation that, as an activation method, does not give information about which regions are critical to a task, but rather indicates regions that participate in a task and, thus, is not ideal for predicting postoperative deficits. Electrophysiological methods reveal neuronal activity more directly, with good temporal resolution, but source localization can be difficult. Subdural electrocorticography has improved spatial resolution and allows artifact-free recording of high-frequency activity, but the significance of ESA gamma augmentation is still under investigation. ECS mapping during resection, not used here, can safeguard against postoperative deficits, but it requires technical and operative staff experienced in the technique and the risk of afterdischarge elicitation remains. Though motor mapping may be done via ECS with the patient under anesthesia, other types of mapping may require a cooperative patient. ESA using implanted electrodes may prove especially useful for mapping language in patients who could not tolerate an awake craniotomy. Because none of these methods offers an ideal map of cortical functional anatomy, it is important to consider their relative strengths and limitations when interpreting results. Complementary methods based on different physiological mechanisms may provide richer functional data, allowing resection of lesions otherwise deemed off-limits.
Acknowledgments The authors thank Lauren Moo, M.D., for functional magnetic resonance imaging; Frederick Lenz, M.D.,
Ph.D., for neurosurgical management; and Lei Hao, Ph.D., for technical assistance. This work was supported in part by the National EpiFellows Foundation (H.E.K.), the Epilepsy Foundation of America/Abbot Laboratories (H.E.K.), and NINDS R01-NS40596 (N.E.C.).
References [1] Nii Y, Uematsu S, Lesser RP, Gordon B. Does the central sulcus divide motor and sensory functions? Cortical mapping of human hand areas as revealed by electrical stimulation through subdural grid electrodes. Neurology 1996;46:360–7. [2] Uematsu S, Lesser R, Fisher RS, et al. Motor and sensory cortex in humans: topography studied with chronic subdural stimulation. Neurosurgery 1992;31:59–71, discussion 71–2. [3] Nudo RJ, Plautz EJ, Frost SB. Role of adaptive plasticity in recovery of function after damage to motor cortex. Muscle Nerve 2001;24:1000–19. [4] Duffau H. Acute functional reorganisation of the human motor cortex during resection of central lesions: a study using intraoperative brain mapping. J Neurol Neurosurg Psychiatry 2001;70:506–13. [5] Moo LR, Slotnick SD, Krauss G, Hart J. A prospective study of motor recovery following multiple subpial transections. NeuroReport 2002;13:665–9. [6] Lesser RP, Luders H, Klem G, et al. Extraoperative cortical functional localization in patients with epilepsy. J Clin Neurophysiol 1987;4:27–53. [7] Luders H, Lesser RP, Dinner DS, Morris HH, Wyllie E, Godoy J. Localization of cortical function: new information from extraoperative monitoring of patients with epilepsy. Epilepsia 1988;29(Suppl 2):S56–65. [8] Crone NE, Miglioretti DL, Gordon B, Lesser RP. Functional mapping of human sensorimotor cortex with electrocorticographic spectral analysis: II. Event-related synchronization in the gamma band. Brain 1998;121(Pt. 12):2301–15. [9] Crone NE, Hao L, Hart Jr J, et al. Electrocorticographic gamma activity during word production in spoken and sign language. Neurology 2001;57:2045–53. [10] Pfurtscheller G, Graimann B, Huggins JE, Levine SP, Schuh LA. Spatiotemporal patterns of beta desynchronization and gamma synchronization in corticographic data during self-paced movement. Clin Neurophysiol 2003;114:1226–36. [11] Crone NE, Boatman D, Gordon B, Hao L. Induced electrocorticographic gamma activity during auditory perception: Brazier Award-winning article, 2001. Clin Neurophysiol 2001; 112:565–82. [12] Duffau H, Sichez JP, Lehericy S. Intraoperative unmasking of brain redundant motor sites during resection of a precentral angioma: evidence using direct cortical stimulation. Ann Neurol 2000;47:132–5. [13] Duffau H, Denvil D, Capelle L. Long term reshaping of language, sensory, and motor maps after glioma resection: a new parameter to integrate in the surgical strategy. J Neurol Neurosurg Psychiatry 2002;72:511–6. [14] Lado FA, Legatt AD, LaSala PA, Shinnar S. Alteration of the cortical motor map in a patient with intractable focal seizures. J Neurol Neurosurg Psychiatry 2002;72:812–5. [15] Nathan SS, Sinha SR, Gordon B, Lesser RP, Thakor NV. Determination of current density distributions generated by electrical stimulation of the human cerebral cortex. Electroencephalogr Clin Neurophysiol 1993;86:183–92.
Case Report
Multimodal functional mapping of sensorimotor cortex prior to resection of an epileptogenic perirolandic lesion Heidi E. Kirsch,a,* Jehuda P. Sepkuty,b and Nathan E. Croneb a
UCSF Epilepsy Center, Department of Neurology, University of California San Francisco School of Medicine, San Francisco, CA, USA b Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA Received 15 January 2004; revised 5 February 2004; accepted 10 February 2004 Available online 19 March 2004
Abstract The effects of chronic epileptogenic lesions on functional anatomy are under debate. Our recent experience during mapping and resection of a lesion in sensorimotor cortex supports the idea that epileptogenic lesions may prompt development of alternate cortical motor representations. Multimodal mapping may uncover alternate areas of functionality that make surgery feasible even when conventional neuroanatomy suggests otherwise. Newer methods such as electrocorticographic spectral analysis may complement traditional electrical cortical stimulation mapping. Ó 2004 Elsevier Inc. All rights reserved. Keywords: Functional mapping; Epilepsy surgery; Electrocorticography; Electrocorticographic spectral analysis; Cortical plasticity; Motor cortex
1. Introduction Evidence from electrical cortical stimulation (ECS) mapping suggests that sensorimotor topography may vary widely [1,2]. In addition, chronic cortical lesions may lead to reorganization of functional anatomy, as demonstrated in primates and in humans [for a review, see 3]. This reorganization presumably occurs by compensatory cortical synaptic reorganization like that observed after experimental manipulation of afferent pathways in animals. With slow-growing lesions of sensorimotor cortex, intraoperative ECS has been used to guide excision to spare function. In some cases, multiple representations for the upper extremity have been identified that were not apparent with ECS before resection, but were demonstrated immediately afterward, suggesting that alternate cortical representations were available [e.g., 4]. Before resection near essential cortical regions, identification of alternate cortical representations might mitigate postoperative deficits.
* Corresponding author. Fax: 1-415-252-2837. E-mail address: [email protected] (H.E. Kirsch).
1525-5050/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2004.02.001
This principle is illustrated by a patient with intractable epilepsy from a chronic perirolandic lesion. Prolonged EEG monitoring showed ictal onset in sensorimotor cortex, complicating surgical planning. Ictal electrocorticographic (ECoG) recordings located the epileptogenic zone in sensorimotor regions identified through extraoperative ECS mapping. However, functional mapping with multiple complementary methods revealed additional surrounding cortical regions that had similar motor function. This allowed us to postulate that alternate cortical representations might minimize the risk of postlesionectomy deficits.
2. Case Our subject was an 18-year-old right handed man with multiple cavernous angiomas (Fig. 1) and intractable simple partial seizures of the right arm, onset at C1/C3/ CP3 scalp electrodes. He also had rare complex partial seizures without lateralizing features (presumably from another source). He underwent implantation of subdural electrodes (platinum–iridium; 2.3-mm-diameter exposed surface; 1-cm center-to-center spacing; Ad-Tech, Racine, WI, USA) to better define his seizure focus (Fig. 2).
408
Case Report / Epilepsy & Behavior 5 (2004) 407–410
stant-current electrical stimulation (biphasic square waves, 300-ls pulse width, 50 Hz, 10–15 mA, 5-s duration) was delivered by a Grass S12 stimulator (Grass Instruments, Quincy, MA, USA) between pairs of adjacent electrodes (bipolar ECS) and between individual electrodes and distant, uninvolved reference electrodes (unipolar ECS). A standard battery of motor tasks were performed during ECS (for a description of the battery, see, e.g., [1]). Signs of functional interference were recorded on videotape and visually interpreted by clinical observers; interference was termed ‘‘positive’’ if stimulation evoked movement and ‘‘negative’’ if it slowed or arrested movement [7]. 2.3. ECoG somatosensory evoked potentials
Fig. 1. T1 axial magnetic resonance image of patientÕs brain; note multiple cavernous angiomas, including the ictal source (white arrow) in the left rolandic region.
A Grass S11 stimulator delivered 300-ms constantcurrent pulses to the right median nerve at motor threshold through wrist surface electrodes (rate ¼ 4.7 Hz, N ¼ 2000) [1]. Signals were averaged over trials with respect to stimulation; N1 (20-ms) and P1 (24-ms) waveforms were used to estimate central sulcus location, and a single moving dipole was modeled using Curry software (Compumedics Neuroscan, El Paso, TX, UAS).
2.1. Neuroimaging 2.4. ECoG spectral analysis (ESA) Preimplantation three-dimensional volumetric MRI was coregistered with postimplantation CT using Curry software (Neurosoft, El Paso, TX, USA) to verify electrode position on cortex; this corresponded to intraoperative digital photography (Fig. 2). Preoperative functional MRI (fMRI) was performed during right-hand complex finger tapping as described by Moo et al. [5]. 2.2. Electrical cortical stimulation mapping ECS mapping was performed according to routine clinical procedures described elsewhere [e.g., 6,7]. Con-
Electrocorticograms were digitally recorded (1000-Hz sampling) during self-paced button press (subject pressed at approximately 10-s intervals without counting). Event-related augmentation of power in an 80–100 Hz ‘‘high gamma’’ band was used to index cortical activation. This index has been validated for visual–motor tasks [8], word production tasks [9], and the task used here [10]. Gamma power augmentation was quantified by digital bandpass (80–100 Hz) filtering and squaring of the ECoG signal, followed by segmentation (100-ms epochs with 50% overlap) and averaging of the resulting
Fig. 2. Intraoperative photographs before and after subdural electrode implantation and after lesion resection. Electrodes are overlying the left central region (arrows point to anatomic central sulcus) and are numbered following indicated sequence. The orientation of the photographs is such that the patientÕs nose is to the viewerÕs upper right, and the top of the patientÕs head is to the viewerÕs lower right.
Case Report / Epilepsy & Behavior 5 (2004) 407–410
power values across trials (N ¼ 50); statistical analyses identified electrodes where gamma band power in poststimulus epochs and prestimulus (baseline) epochs differed significantly (for a description of the analytical method, see [11]). The patientÕs typical simple partial seizures at the right wrist and elbow, with variable involvement of fingers and shoulder, were recorded. Ictal subdural electrocorticography demonstrated onset from cortex overlying an angioma on the anterior lip of a left frontoparietal sulcus. Preoperative fMRI showed that right complex finger tapping activated cortex immediately posterior to the lesion (Fig. 3). ECS of the epileptogenic zone caused right finger, hand, and proximal arm movements (i.e., ‘‘positive interference’’). However, ECS of cortical tissue in a zone surrounding the lesion in all directions and extending up to as far as 3 cm posterior to the lesion and 2 cm inferior to the lesion also caused finger, hand, and proximal arm movements. Stimulation of electrodes 1 cm anterior and 1 cm anterosuperior to the lesion interfered with finger, hand, and proximal arm movements reliably (i.e., ‘‘neg-
409
ative interference’’), but stimulation at some of these electrodes also elicited clonic movements of the face, eyelids, and mouth (i.e., both positive and negative interference). Phase reversal of N1 and P1 of median SEPs (via ECoG) occurred 0.5 cm posterior to the lesion, and calculated equivalent dipoles for these potentials localized to the same spots. ESA high gamma augmentation during self-paced button press occurred maximally in electrodes inferior and posterior to the angioma. The epileptogenic lesion and the overlying cortex were resected. Postoperatively, the patient had mild proximal weakness of the right arm, confined to shoulder shrug, but fine finger movements were unchanged from baseline. Subtle signs of distal pyramidal weakness, such as reduced fluidity of fine finger movements and finger extensor weakness, were absent, as were pronator drift and orbit signs. A week later, strength and dexterity had returned fully to baseline. Six months later, he was free of simple partial seizures, though he continued to have rare complex partial seizures.
3. Discussion
Fig. 3. Cortical surface rendering of preoperative MRI, with subdural electrodes from postoperative CT scan superimposed. As in Fig. 2, electrodes are numbered starting from the upper right hand corner of the array; electrodes 8 and 64 are indicated. Yellow lightning bolts indicate the region of seizure onset. The purple shading indicates the approximate surface projection of the underlying angioma. The light blue shading indicates the approximate region of fMRI activation. The black arrow indicates the anatomic central sulcus, as in Fig. 2. Electrode color indicates the results of ECS mapping. For simplicity, only unipolar right upper extremity results are shown (reference electrode is 8 or 64). Red¼ evoked movement (‘‘positive response’’), green ¼ no deficit with ECS. Slowed or arrested movement (‘‘negative response’’) is not shown here, as it overlapped red regions extensively. Stimulation at the yellow electrode was followed by an evoked seizure in the right hand. Small yellow dots indicate evoked clonic movements in the right upper extremity with bipolar stimulation between adjacent electrode pairs. The blue line indicates the border of the right median SEP phase reversal. Magenta circles indicate regions of maximal 80- to 100-Hz augmentation during a self-paced button press with the right thumb; the size of the circle corresponds to the degree of augmentation seen at a given electrode.
Because the subjectÕs seizure focus was associated with a lesion in the motor strip, detailed motor mapping was necessary to assess the risks of resection. We found a hand motor representation larger than expected by anatomic landmarks alone. This suggested that cortical reorganization had taken place, perhaps due to chronic hemorrhage and/or epileptogenic activity associated with the lesion. ECS mapping in our subject showed multiple areas of similar motor representation; given the expansion and apparent redundancy of hand and finger sensorimotor regions, it was difficult to know which areas might adequately preserve hand motor function if others were resected. The mechanism for the apparent expansion of motor representation is unknown. Duffau posits that there are, in normal individuals as well as those with chronic lesions, multiple redundant circuits for the same motor function that exist within motor cortex [4,12], as well as in somatosensory and language cortex [13]. These redundant cortical representations are latent and capable of being acutely ‘‘unmasked’’ after resection of motor cortex. Another possibility is that chronic epileptiform activity suppressed the normal function of cortex overlying the lesion, and that neighboring regions took over its function. Such changes in the topography of sensorimotor function in the presence of ongoing epileptiform activity without changes in the underlying structural lesion were reported by Lado et al. [14] in a case of serial cortical stimulation mapping with an interval of several years. In our subject, this possibility could not be confirmed. Although cortical stimulation mapping showed multiple areas of similar motor representation, it was difficult to
410
Case Report / Epilepsy & Behavior 5 (2004) 407–410
know which areas might adequately preserve hand motor function if others were resected. In addition, there was no consistent difference in the motor interference produced by ECS between cortex overlying the lesion and neighboring cortex. We were fortunate, however, to have other types of data relying on different mechanisms. Two nonlesional mapping methods, functional MRI and ESA, indicated that regions within ECS-defined cortical hand area specifically activated with voluntary hand movement tasks and did not overlap with the epileptogenic region. These smaller regions were spared during surgical resection in hopes of providing seizure freedom without motor deficit. Although we did not map motor function after our subjectÕs resection, the lack of significant postoperative motor deficit suggests that spared regions were sufficient for hand function. Proximal weakness was confined to shoulder shrug, which recovered acutely as is typical postoperatively for such deficits, perhaps due to bihemispheric representation for such regions. This case demonstrates the potential benefits of using complementary functional mapping methods. Although the effective current density during ECS is circumscribed [15], it may have unforeseen transsynaptic effects on functionally connected cortex. fMRI provides a noninvasive, but indirect, measure of cortical activation that, as an activation method, does not give information about which regions are critical to a task, but rather indicates regions that participate in a task and, thus, is not ideal for predicting postoperative deficits. Electrophysiological methods reveal neuronal activity more directly, with good temporal resolution, but source localization can be difficult. Subdural electrocorticography has improved spatial resolution and allows artifact-free recording of high-frequency activity, but the significance of ESA gamma augmentation is still under investigation. ECS mapping during resection, not used here, can safeguard against postoperative deficits, but it requires technical and operative staff experienced in the technique and the risk of afterdischarge elicitation remains. Though motor mapping may be done via ECS with the patient under anesthesia, other types of mapping may require a cooperative patient. ESA using implanted electrodes may prove especially useful for mapping language in patients who could not tolerate an awake craniotomy. Because none of these methods offers an ideal map of cortical functional anatomy, it is important to consider their relative strengths and limitations when interpreting results. Complementary methods based on different physiological mechanisms may provide richer functional data, allowing resection of lesions otherwise deemed off-limits.
Acknowledgments The authors thank Lauren Moo, M.D., for functional magnetic resonance imaging; Frederick Lenz, M.D.,
Ph.D., for neurosurgical management; and Lei Hao, Ph.D., for technical assistance. This work was supported in part by the National EpiFellows Foundation (H.E.K.), the Epilepsy Foundation of America/Abbot Laboratories (H.E.K.), and NINDS R01-NS40596 (N.E.C.).
References [1] Nii Y, Uematsu S, Lesser RP, Gordon B. Does the central sulcus divide motor and sensory functions? Cortical mapping of human hand areas as revealed by electrical stimulation through subdural grid electrodes. Neurology 1996;46:360–7. [2] Uematsu S, Lesser R, Fisher RS, et al. Motor and sensory cortex in humans: topography studied with chronic subdural stimulation. Neurosurgery 1992;31:59–71, discussion 71–2. [3] Nudo RJ, Plautz EJ, Frost SB. Role of adaptive plasticity in recovery of function after damage to motor cortex. Muscle Nerve 2001;24:1000–19. [4] Duffau H. Acute functional reorganisation of the human motor cortex during resection of central lesions: a study using intraoperative brain mapping. J Neurol Neurosurg Psychiatry 2001;70:506–13. [5] Moo LR, Slotnick SD, Krauss G, Hart J. A prospective study of motor recovery following multiple subpial transections. NeuroReport 2002;13:665–9. [6] Lesser RP, Luders H, Klem G, et al. Extraoperative cortical functional localization in patients with epilepsy. J Clin Neurophysiol 1987;4:27–53. [7] Luders H, Lesser RP, Dinner DS, Morris HH, Wyllie E, Godoy J. Localization of cortical function: new information from extraoperative monitoring of patients with epilepsy. Epilepsia 1988;29(Suppl 2):S56–65. [8] Crone NE, Miglioretti DL, Gordon B, Lesser RP. Functional mapping of human sensorimotor cortex with electrocorticographic spectral analysis: II. Event-related synchronization in the gamma band. Brain 1998;121(Pt. 12):2301–15. [9] Crone NE, Hao L, Hart Jr J, et al. Electrocorticographic gamma activity during word production in spoken and sign language. Neurology 2001;57:2045–53. [10] Pfurtscheller G, Graimann B, Huggins JE, Levine SP, Schuh LA. Spatiotemporal patterns of beta desynchronization and gamma synchronization in corticographic data during self-paced movement. Clin Neurophysiol 2003;114:1226–36. [11] Crone NE, Boatman D, Gordon B, Hao L. Induced electrocorticographic gamma activity during auditory perception: Brazier Award-winning article, 2001. Clin Neurophysiol 2001; 112:565–82. [12] Duffau H, Sichez JP, Lehericy S. Intraoperative unmasking of brain redundant motor sites during resection of a precentral angioma: evidence using direct cortical stimulation. Ann Neurol 2000;47:132–5. [13] Duffau H, Denvil D, Capelle L. Long term reshaping of language, sensory, and motor maps after glioma resection: a new parameter to integrate in the surgical strategy. J Neurol Neurosurg Psychiatry 2002;72:511–6. [14] Lado FA, Legatt AD, LaSala PA, Shinnar S. Alteration of the cortical motor map in a patient with intractable focal seizures. J Neurol Neurosurg Psychiatry 2002;72:812–5. [15] Nathan SS, Sinha SR, Gordon B, Lesser RP, Thakor NV. Determination of current density distributions generated by electrical stimulation of the human cerebral cortex. Electroencephalogr Clin Neurophysiol 1993;86:183–92.