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Innovation in Neurosurgery: The Concept of Cognitive Mapping
Innovation in Neurosurgery Special Section
Innovation in Neurosurgery: The Concept of Cognitive Mapping Marco Rossi1, Marco Conti Nibali1, Fabio Torregrossa2, Lorenzo Bello1, Giovanni Grasso2
In recent years, advances in cortical-subcortical mapping, intraoperative neurophysiology, and neuropsychology have increased the ability to remove intrinsic brain tumors, expanding indications and maximizing the extent of resection. This has provided a significant improvement in progression-free survival, time of malignant transformation (in low-grade gliomas), and overall survival. Although current techniques enable preservation of language and motor functions during surgery, the maintenance of a complex set of functions defined with the term cognition is not always achievable. Cognition is defined as every neural process underlying a high human function and includes motor haptic and visuospatial functions, memory, social interactions, empathy, and emotions. In this regard, an extensive preoperative and postoperative neuropsychological evaluation is strongly suggested to assess cognitive impairment due to tumor growth, to assess surgical result, and to plan cognitive rehabilitation. This article discusses the main recent innovations introduced for cognitive mapping with the aim to preserve cognitive functions, which are essential to maintain a high quality of life.
INTRODUCTION
M
odern neurosurgical oncology has the goal of maximal tumor resection while at the same time maintaining the patient’ functional integrity, which ultimately defines the so-called onco-functional balance. This has been feasible at the time of surgery by the use of brain mapping techniques, comprehensive use of intraoperative neurophysiology and
neuropsychology.1-3 The surgeon initially performs cortical mapping, to locate functional cortical sites to be spared and to identify negative cortical sites, where to start with the resection. At the subcortical level, the resection is continued while brain mapping is performed until functional boundaries are encountered at the tumor periphery, where tumor removal is stopped. Traditionally, brain mapping has been restricted to pure motor or language functions.4 In the awake or asleep setting, according to the clinical needs, surgeons ask the patient to perform a series of language tasks, while the use of intraoperative neurophysiologic stimulation is locating the sites where interferences are evoked; similarly, overt or electromyography-detected movements can be elicited by the use of direct cortical or subcortical stimulation. However, besides language or pure motor evaluation, full functional preservation requires the maintenance of a complex setup of functions, which are collected under the term of cognition.5 Cognition comprises every neural process that subserves a high human function and includes motor haptic and visuospatial functions, memory, social interactions, empathy, and emotions. In recent years, advances the development in surgical techniques and in the knowledge of brain functional organization have progressively increased surgeons’ ability to remove intrinsic brain tumors, expanding indications and improving the extent of resection. This has been associated with increases in progressionfree survival, malignant transformation time (in low-grade gliomas [LGGs]), and ultimately overall survival.2,3,6-10 Occurring in parallel with these increases, more attention has been increasingly paid to preserve higher cognitive function with the aim of preserving full patient functional integrity and particularly to maintain their quality of life. In fact, although language and motor functions have been mapped and preserved during surgery, many patients reported after surgery the onset of a wide spectrum of cognitive impairments, which ultimately affected their ability to perform routine daily life activities and especially demanding work activities.11 This situation reflects the pioneer status of work in the
Key words Cognition - Eloquent areas - Glioma surgery - Neuropsychological tests
From the 1Neurosurgical Oncology Unit, Department of Oncology and Hemato-Oncology, Università degli Studi di Milano and Humanitas Research Hospital, Istituto di Ricerca e Cura a Carattere Scientifico, Milan; and 2Neurosurgical Clinic, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, Palermo, Italy
Abbreviations and Acronyms DES: Direct electrical stimulation fMRI: Functional magnetic resonance imaging LGG: Low-grade glioma
Citation: World Neurosurg. (2019) 131:364-370. https://doi.org/10.1016/j.wneu.2019.06.177
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To whom correspondence should be addressed: Marco Rossi, M.D. [E-mail: [email protected]]
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field of brain mapping, as it has been reported in a recent systematic review of brain mapping literature that the number of scientific articles focused on mapping and monitoring of functions different from language or motor is still quite limited.4 Of 232 studies analyzed, 207 were mainly focused on language mapping, and <20 evaluated other cognitive domains. A key point of an innovative approach to functional neurosurgery is the adoption of extensive neuropsychological testing in the preoperative evaluation of patients and in their postoperative follow-up. Most deficits related to high cognitive function impairment are quite subtle and usually are not detected during standard neurologic examination and are rarely described clearly by patients or relatives. From this basis, it is recommended to administer before surgery an extensive battery of neuropsychological tests capable of covering all cognitive domains (language, visuospatial abilities, executive function, praxis, fluid intelligence) to detect any preoperative disturbances induced by the growing tumor that are usually undetected by standard testing. The same battery of tests should be administered after surgery and during follow-up to evaluate not only the functional results of surgery but also the impact of cognitive rehabilitation, with the aim of developing and implementing possible strategies to compensate for permanent cognitive deficits.12,13 Despite the need to maximize functional preservation during surgery, the increase in the number of intraoperative tests requested to expand the number of functions to be mapped and preserved may result in an increase in the mapping time requested during the surgical intervention. Although awake procedures are usually well tolerated by patients,14 it is also well known from routine clinical practice that patients’ cooperation usually dramatically decreases with the increase in the surgical and mapping time and with the level of difficulties of the administered test. Hence, it is mandatory to carefully
Figure 1. Intraoperative tasks recommended for performing cognitive or advanced motor mapping. The tasks have been grouped according to the lobe in which they are usually applied and represented on a
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select the intraoperative tasks to be performed according to the site of the tumor having in the mind the type of networks possibly affected or being encountered during the various phases of the resection, tailoring the mapping based on the results of preoperative neuropsychological evaluation and the specific needs of patients. In fact, the best results are obtained when an approach tailored to the individual patient is used. As a consequence, it could be advisable to start the surgery with a core set of basic tests to be performed as soon as possible during the awake phase, with a second set of advanced tests to be performed if the patient is still fully cooperative after the first set. The second set of tests should be selected according to the possible functional networks encountered and taking into consideration specific expectations of individual patients. In this article, we discuss some of the recent innovations introduced during motor and cognitive mapping that have produced a significant improvement in the global functional profile of patients at individual levels. Most of the investigations and tasks described are fully available in the literature and can be considered as ready to be used (Figure 1). INNOVATION IN MOTOR MAPPING Haptic Control Along with language, motor function is probably the main neurologic function to be preserved during neurosurgical procedures. Motor output during stimulation of primary motor area and descending motor pathways has been described since the first surgical procedures performed in awake surgery. In past years, 2 main stimulation techniques, low-frequency stimulation and high-frequency stimulation,1 were introduced and developed to identify the primary motor cortex and the corticospinal tract. Both techniques are widely diffuse and are very effective in
three-dimensional reconstruction of a brain template. Citations of references for each task are provided. RME, Reading the Mind in the Eyes test; PPT, Pyramids and Palm Trees test.
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preserving basic motor function, with a reported rate of permanent postoperative deficit of <5% in most series.15,16 Despite the low rate of permanent motor deficits, particularly in cases where a supratotal resection was achieved, additional motor deficits were detected when a more detailed motor function assessment was performed. A large number of patients treated for lesions located within 2 cm of the central sulcus (either anteriorly or posteriorly) experienced hand apraxia after surgery, despite preserved motor function. Apraxia is the disturbance in timing, sequencing, and spatial organization of movements that render a patient unable to perform daily activities and to return to work at his or her previous level. Rossi et al.17 recently proposed a new intraoperative test based on a tool (called the screwdriver) capable of investigating haptic control of hand movements during surgical procedures for tumor removal. The application of this intraoperative test during awake surgery has been reported to dramatically decrease the prevalence of hand apraxia after surgery, improving patients’ quality of life as well as facilitating their return to work.
Figure 2. Representative case of a patient with a right frontal low-grade glioma who underwent surgery according to functional boundaries in whom advanced motor (haptic) and cognitive mapping was applied at cortical and subcortical levels to guide tumor removal and define subcortically the margins of resection. (A) Preoperative fluid attenuated inversion recovery images (axial, sagittal, and coronal) show a hyperintense lesion in the right frontal lobe, involving the superior and middle frontal gyrus, just anteriorly to the precentral gyrus. Surgery was performed under
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During the test, the patient is invited to perform a rotational movement with the screwdriver tool, while the surgeon by means of direct electrical stimulation (DES) investigates various brain sites at cortical and subcortical levels to identify the sites involved in haptic control. When an arrest of the movement or an alteration of the pattern of the ongoing movement is reported by a neuropsychologist, the site is defined as eloquent for haptic control and preserved during resection. Thanks to this approach, cortical and subcortical networks involved in precise motor control, the so-called praxis network, can be identified and preserved, avoiding the development of hand apraxia in the postoperative period (Figure 2). Administration of the test increases the surgical time of brain mapping by an average of only 12 minutes and does not change the extent of resection. This last point can be explained by the fact that the sites involved in the praxis network are quite discrete, and their preservation, although of functional relevance, does not change on average the degree of surgical resection.17 Besides the relevant clinical impact previously described, this new tool is able to give new insights in the role of nonprimary
asleep-awake-asleep anesthesia with neurophysiologic and neuropsychological mapping and monitoring. (B) The screwdriver test was applied to define the praxis network, which represented the posterior boundary of the resection. The Stroop test was applied to identify the corticostriatal frontal network and represented the inferior margin of the resection. Intraoperative sites of interference recorded for each test are reported and overlapped in the postoperative T1 postgadolinium scan (axial, sagittal, and coronal).
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motor areas in motor control. It also improves knowledge of the functional organization of the hand-knob region at the cortical and subcortical levels. Vigano et al.,18 analyzing the intraoperative neurophysiologic data registered during surgery while the patient was performing the haptic test, showed a rostrocaudal gradient of cortical excitability and different motor interferences during the execution of the task depending on the sites of stimulation. These physiologic data along with tractography reconstruction of the subcortical connectivity (particularly at the level of U-fibers) in the hand-knob area suggest the existence of different connection patterns in relation to the type of interference observed. These data may further expand knowledge of the functional organization of this area and suggest the development of further intraoperative investigational tools to assess it properly. Negative Motor Areas The role of some of the so-called nonprimary areas in the modulation of motor functions has been described by Duffau’s group.19 These investigators described cortical and subcortical sites located mainly in the anterior parietal lobe, which when stimulated by means of DES cause inhibition of voluntary movement. They located these negative motor responses in the postcentral gyrus and in the white matter located deep to the supramarginal gyrus and described a frontoparietal network as the main structure involved in modulating motor control. Furthermore, Rech et al.20 provided the first probabilistic map of negative motor areas of the upper limb and face processing data of 117 patients who underwent awake surgery for diffuse LGG. According to the above-mentioned study, negative motor areas are not randomly distributed, as previously suggested,21 because they are structured cortically along the dorsal and ventral premotor cortex.20 The preservation of such sites was associated with the maintenance of full motor control. In a recent study, Desmurget et al.22 confirmed and further analyzed the phenomenon of negative motor sites in the parietal lobe. The authors described in 16 patients several cortical sites located in the inferior and superior parietal lobule that when simulated by DES during awake surgery caused an inhibition of ongoing voluntary movement without any conscious feeling by the patients. They also reported the electromyographic analysis of the negative motor responses, showing different patterns of motor interference. The clinical significance of such sites is still a matter of investigation. INNOVATION IN COGNITIVE MAPPING Executive Functions Executive functions are a set of supramodal abilities involved in controlling cognitive processes and modulating behavioral changes that take place when someone wants to reach specific goals.23 The executive functions have an important role in everyday activities, such as focusing on a specific task, as well as work activities or social interactions. An impairment in this cognitive domain following a tumor resection has a negative impact on quality of life, as reported by many patients, despite intact neurologic and basic neuropsychological examinations. The neural networks involved in these complex functions are less known compared with the network subserving language
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production and comprehension. Most of the data come from functional magnetic resonance imaging (fMRI) or other functional imaging studies, suggesting a bilateral organization of the networks, mainly involving the frontocorticostriatal region, connecting prefrontal cortices and the basal ganglia.24-26 However, the full anatomic description of this cortical-subcortical network is still not completely available. This lack of knowledge may be one of the reasons why the use of intraoperative mapping and monitoring of higher cognitive function is not prevalent in the operating room. In addition, most of the tests available in the neuropsychological armamentarium are too long or too difficult and not suitable for intraoperative administration. Puglisi et al.23 recently reported an effective intraoperative test designed to map executive functions. In their article, the authors described a simplified version of the Stroop test,27,28 a well-known neuropsychological test used to assess interferences with executive functions, which can be easily administered intraoperatively in awake conditions. They demonstrated the efficacy of the test in detecting subcortical sites in the nondominant frontal lobe, which when spared during surgery preserved the executive functions (Figure 2). Starting from this evidence, further investigation suggested the involvement of the corticostriatal network connecting prefrontal cortices and basal ganglia in subserving such complex functions.23 Mentalization In recent decades, increasing attention has been focused on the preservation of social abilities in patients undergoing resection of intra-axial brain tumors to fully preserve their quality of life. Patients with LGGs are mostly young and after gross total resection or even supratotal resection may have a very long life expectancy. In this specific setting, the preservation of patients’ abilities to communicate and develop normal interactions and build relationships with other people and to continue their previous roles in their families is of significant importance. Social abilities are a complex set of skills, and social neuroscience describes mentalization as one of the key components involved in the ability to interact with others by understanding their mental state.29 An intraoperative adaptation of the neuropsychological test Reading the Mind in the Eye has been developed for intraoperative use during awake procedures. When applied intraoperatively during surgical removal for intrinsic brain tumors, with the aid of DES, the test allowed the surgeon to identify various sites in the nondominant frontal lobe at both cortical and subcortical levels that when spared from resection were associated with the maintenance of mentalization abilities.30 The initial report on the use of this test at the cortical level suggested involvement of the nondominant inferior frontal cortex (pars triangularis and pars opercularis).29 A further report on the use of the intraoperative test at the subcortical level indicated the right arcuate fasciculus as one of the main circuits possibly involved in mediating this complex mental process.31 Starting from the data acquired during intraoperative mentalization testing, Yordanova et al.32 depicted the involvement of a larger network applying task-based fMRI and resting-state fMRI. The intraoperative results of the study confirmed the key role of the right inferior and middle frontal gyrus, whereas resting-state fMRI suggested also the involvement
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of the contralateral frontal lobe and the right posterior temporal gyrus and right inferior parietal lobule. Preservation of this largescale neural network in the right hemisphere should avoid social cognition disorders in the postoperative period, preserving social abilities of patients and ensuring the maintenance of full quality of life. Semantic Association Traditionally, language mapping is performed while the patient is counting or naming. However, language is not restricted to these 2 basic components. The term semantic association refers to the ability to associate similar items together, which is one of the crucial modalities of human language. This component of human language has been described to be mediated by the left ventral stream, mainly the inferior-fronto-occipital fasciculus. The implementation of such a test increased the efficacy of the mapping and patients’ performances after surgery.33 However, semantic processing of information also includes a nonverbal modality. In the past, the anatomo-functional network subserving nonverbal processing functions was not fully identified; a few studies based on fMRI data showed a bilateral activation during execution of a test based on pictures.34 When applying the Pyramids and Palm Trees test, a well-described visual nonverbal semantic association test used in neuropsychological examinations,35 during surgical removal of right hemisphere tumors performed under awake conditions, Herbet et al.33 described interferences in semantic processing due to stimulation of the right inferior fronto-occipital fasciculus. Despite this encouraging evidence of the role of the right inferior fronto-occipital fasciculus in nonverbal semantic processing, the clinical impact of the preservation of the sites giving interferences during stimulation while the patient was performing this task is not fully known, and more work needs to be done in this direction. Visuospatial Abilities Visuospatial abilities include all the mental skills needed to identify and analyze a space and to interact with it. The most relevant clinical manifestation of deficits in visuospatial abilities is spatial neglect, a clinical condition in which the patient, in the absence of visual field or sensorimotor deficit, is unable to explore space contralateral to the affected side. Spatial neglect was described first in stroke literature as a result of parietal stroke. In recent decades, attention has also been given to visuospatial abilities in patients undergoing surgery for resection of parietal lobe tumors. Initially, a test called line bisection was proposed,36 but more recently another neuropsychological test adapted for the intraoperative setting has been published, the target cancellation task, with similar results.37 In the target cancellation task, distinct simple shapes are shown to patients on a handheld touchscreen tablet with a vertical line dividing the screen into 2 equal halves. Patients are trained beforehand to cancel with a swiping movement of a finger the specifically targeted shape in both the right and the left fields. The main constraint of the administration of these tests is related to their repeatability, particularly because the test is generally administered when the patient is lying in a lateral position.
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ADJUNCT FACTORS ASSOCIATED WITH COGNITION IMPAIRMENT It has been pointed out that besides preoperative and postoperative evaluation, tumor-related factors can affect cognitive dysfunction in patients with gliomas, particularly LGGs. The tumor itself adversely affects neurobehavioral function in patients with LGGs.38 Tumor localization seems to be one of the most important factors. In this regard, tumors located in the dominant temporal or frontal area usually affect language function owing to the organization of linguistic function.39 Accordingly, neoplastic lesions infiltrating the uncinate fasciculus39,40 provide a higher grade of language impairment than tumors located near the arcuate fasciculus.41 In this regard, radiotherapy has been shown to strongly affect the quality of life of patients through deleterious effects on brain parenchyma resulting in cognitive deficits and dementia.42,43 In this regard, several differences in mean cognitive function scores between patients with LGGs who received radiotherapy and patients who did not have been reported.44 Variables such as overall dose and treatment volume and the size of the fraction dose have been largely identified as responsible factors for the development of late neurotoxicity.45 In particular, radiotherapy given in daily fractions >2 Gy has been shown to be harmful for the normal surrounding brain over time, in contrast to conventional external-beam radiotherapy. A subsequent study investigating radiologic and cognitive sequelae in patients with LGGs at a mean follow-up of 12 years after radiotherapy showed a progressive decline in attentional functioning, including patients who received fraction doses regarded as safe (2 Gy).46 These cognitive deficits were also associated with radiologic abnormalities.46 Based on the evidence that radiotherapy affects cognitive function, including in the long run, the use of this therapeutic strategy in LGG should be delayed as much as tumor progression allows and tempered with the progression of the tumor. Finally, clinical evidence suggests that medical treatments can affect cognitive function. For instance, the use of antiepileptics has been associated with poorer objectively measured and selfreported cognitive function compared with patients in whom antiepileptics were not used.44 However, this issue requires further investigation before a firm conclusion can be established. CONCLUSIONS Recent advances in surgical techniques have expanded the indications for and increased the extent of resection of intrinsic brain tumors, producing a significant improvement in progression-free survival, time of malignant transformation (in low-grade gliomas), and overall survival. This significant change in the natural history of intrinsic brain tumors has occurred in parallel with the need to increase patients’ full functional integrity. Patients are surviving longer in good clinical condition, but at the same time are experiencing the onset of functional disturbances in addition to the traditionally considered basic motor or language functions. This situation has led to the need to develop additional tests to explore more complex cognitive functions and to develop intraoperative tasks able to identify cortical or subcortical sites possibly involved in these functions.
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The main constraint of this pioneering work is the need to develop tests that are easily administered in the intraoperative setting and are effective in investigating the function for which they were designed. In this article, we described innovative tests that when applied during surgery in awake conditions were able to detect a
REFERENCES 1. Rossi M, Sani S, Nibali MC, Fornia L, Bello L, Byrne RW. Mapping in low-grade glioma surgery: low- and high-frequency stimulation. Neurosurg Clin N Am. 2019;30:55-63. 2. De Witt Hamer PC, Robles SG, Zwinderman AH, Duffau H, Berger MS. Impact of intraoperative stimulation brain mapping on glioma surgery outcome: a meta-analysis. J Clin Oncol. 2012;30: 2559-2565. 3. Duffau H, Taillandier L. New concepts in the management of diffuse low-grade glioma: proposal of a multistage and individualized therapeutic approach. Neuro Oncol. 2015;17:332-342. 4. Ruis C. Monitoring cognition during awake brain surgery in adults: a systematic review. J Clin Exp Neuropsychol. 2018;40:1081-1104. 5. Duffau H. Preserving quality of life is not incompatible with increasing overall survival in diffuse low-grade glioma patients. Acta Neurochir (Wien). 2015;157:165-167. 6. Duffau H. Long-term outcomes after supratotal resection of diffuse low-grade gliomas: a consecutive series with 11-year follow-up. Acta Neurochir (Wien). 2016;158:51-58. 7. Smith JS, Chang EF, Lamborn KR, et al. Role of extent of resection in the long-term outcome of low-grade hemispheric gliomas. J Clin Oncol. 2008; 26:1338-1345. 8. Buckner J, Giannini C, Eckel-Passow J, et al. Management of diffuse low-grade gliomas in adults—use of molecular diagnostics. Nat Rev Neurol. 2017;13:340-351. 9. Grasso G. Extent of resection and survival in glioblastoma multiforme. JAMA Oncol. 2016;2: 1508-1509. 10. Grasso G, Torregrossa F, Leone L. Maximizing the extent of resection in high-grade glioma. World Neurosurg. 2019;123:256-258. 11. Mandonnet E, Sarubbo S, Duffau H. Proposal of an optimized strategy for intraoperative testing of speech and language during awake mapping. Neurosurg Rev. 2017;40:29-35.
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series of functions involved in the maintenance of various cognitive domains. When a functional approach is applied, large resections outside tumor borders are feasible without any additional neurologic or neuropsychological deficit in a large percentage of patients.47
Low Grade Glioma Network multicenter study. Acta Neurochir (Wien). 2013;155:1301-1308. 15. Bello L, Riva M, Fava E, et al. Tailoring neurophysiological strategies with clinical context enhances resection and safety and expands indications in gliomas involving motor pathways. Neuro Oncol. 2014;16:1110-1128. 16. Han SJ, Morshed RA, Troncon I, et al. Subcortical stimulation mapping of descending motor pathways for perirolandic gliomas: assessment of morbidity and functional outcome in 702 cases [e-pub ahead of print]. J Neurosurg. https://doi.org/ 10.3171/2018.3.JNS172494, accessed August 1, 2018. 17. Rossi M, Fornia L, Puglisi G, et al. Assessment of the praxis circuit in glioma surgery to reduce the incidence of postoperative and long-term apraxia: a new intraoperative test. J Neurosurg. 2018;130: 17-27. 18. Vigano L, Fornia L, Rossi M, et al. Anatomofunctional characterisation of the human “handknob”: a direct electrophysiological study. Cortex. 2019;113:239-254. 19. Almairac F, Herbet G, Moritz-Gasser S, Duffau H. Parietal network underlying movement control: disturbances during subcortical electrostimulation. Neurosurg Rev. 2014;37:513-516 [discussion: 516-517]. 20. Rech F, Herbet G, Gaudeau Y, et al. A probabilistic map of negative motor areas of the upper limb and face: a brain stimulation study. Brain. 2019;142:952-965. 21. Borggraefe I, Catarino CB, Remi J, et al. Lateralization of cortical negative motor areas. Clin Neurophysiol. 2016;127:3314-3321. 22. Desmurget M, Richard N, Beuriat PA, et al. Selective inhibition of volitional hand movements after stimulation of the dorsoposterior parietal cortex in humans. Curr Biol. 2018;28:3303-3309.e3. 23. Puglisi G, Sciortino T, Rossi M, et al. Preserving executive functions in nondominant frontal lobe glioma surgery: an intraoperative tool [e-pub ahead of print]. J Neurosurg. https://doi.org/10. 3171/2018.4.JNS18393, accessed September 1, 2018.
12. Duffau H. A new philosophy in surgery for diffuse low-grade glioma (DLGG): oncological and functional outcomes. Neurochirurgie. 2013;59:2-8.
24. Langen M, Leemans A, Johnston P, et al. Frontostriatal circuitry and inhibitory control in autism: findings from diffusion tensor imaging tractography. Cortex. 2012;48:183-193.
13. Duffau H, Mandonnet E. The “onco-functional balance” in surgery for diffuse low-grade glioma: integrating the extent of resection with quality of life. Acta Neurochir (Wien). 2013;155:951-957.
25. Fedorenko E, Duncan J, Kanwisher N. Broad domain generality in focal regions of frontal and parietal cortex. Proc Natl Acad Sci U S A. 2013;110: 16616-16621.
14. Beez T, Boge K, Wager M, et al. Tolerance of awake surgery for glioma: a prospective European
26. Lipszyc J, Levin H, Hanten G, Hunter J, Dennis M, Schachar R. Frontal white matter damage impairs
WORLD NEUROSURGERY 131: 364-370, NOVEMBER 2019
response inhibition in children following traumatic brain injury. Arch Clin Neuropsychol. 2014;29: 289-299. 27. Stuss DT, Floden D, Alexander MP, Levine B, Katz D. Stroop performance in focal lesion patients: dissociation of processes and frontal lobe lesion location. Neuropsychologia. 2001;39:771-786. 28. MacLeod CM. Half a century of research on the Stroop effect: an integrative review. Psychol Bull. 1991;109:163-203. 29. Herbet G, Lafargue G, Moritz-Gasser S, Bonnetblanc F, Duffau H. Interfering with the neural activity of mirror-related frontal areas impairs mentalistic inferences. Brain Struct Funct. 2015;220:2159-2169. 30. Herbet G, Lafargue G, Bonnetblanc F, et al. Inferring a dual-stream model of mentalizing from associative white matter fibres disconnection. Brain. 2014;137:944-959. 31. Nakajima R, Yordanova YN, Duffau H, Herbet G. Neuropsychological evidence for the crucial role of the right arcuate fasciculus in the face-based mentalizing network: a disconnection analysis. Neuropsychologia. 2018;115:179-187. 32. Yordanova YN, Cochereau J, Duffau H, Herbet G. Combining resting state functional MRI with intraoperative cortical stimulation to map the mentalizing network. Neuroimage. 2019;186: 628-636. 33. Herbet G, Moritz-Gasser S, Duffau H. Direct evidence for the contributive role of the right inferior fronto-occipital fasciculus in non-verbal semantic cognition. Brain Struct Funct. 2017;222:1597-1610. 34. Rice GE, Lambon Ralph MA, Hoffman P. The roles of left versus right anterior temporal lobes in conceptual knowledge: an ALE meta-analysis of 97 functional neuroimaging studies. Cereb Cortex. 2015;25:4374-4391. 35. Howard D, Patterson KE. The Pyramids and Palm Trees Test: A Test for Semantic Access from Words and Pictures. Bury St. Edmunds, UK: Thames Valley Test Company; 1992. 36. Vallar G, Bello L, Bricolo E, et al. Cerebral correlates of visuospatial neglect: a direct cerebral stimulation study. Hum Brain Mapp. 2014;35: 1334-1350. 37. Conner AK, Glenn C, Burks JD, et al. The use of the target cancellation task to identify eloquent visuospatial regions in awake craniotomies: technical note. Cureus. 2016;8:e883. 38. Taphoorn MJ, Schiphorst AK, Snoek FJ, et al. Cognitive functions and quality of life in patients with low-grade gliomas: the impact of radiotherapy. Ann Neurol. 1994;36:48-54.
www.journals.elsevier.com/world-neurosurgery
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39. Naidich TP, Hof PR, Gannon PJ, Yousry TA, Yousry I. Anatomic substrates of language: emphasizing speech. Neuroimaging Clin N Am. 2001; 11:305-341. 40. Papagno C, Miracapillo C, Casarotti A, et al. What is the role of the uncinate fasciculus? Surgical removal and proper name retrieval. Brain. 2011; 134:405-414. 41. Zhao Y, Chen X, Wang F, et al. Integration of diffusion tensor-based arcuate fasciculus fibre navigation and intraoperative MRI into glioma surgery. J Clin Neurosci. 2012;19:255-261. 42. Crossen JR, Garwood D, Glatstein E, Neuwelt EA. Neurobehavioral sequelae of cranial irradiation in adults: a review of radiation-induced encephalopathy. J Clin Oncol. 1994;12:627-642. 43. Surma-aho O, Niemela M, Vilkki J, et al. Adverse long-term effects of brain radiotherapy in adult
370
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low-grade glioma patients. Neurology. 2001;56: 1285-1290. 44. Klein M, Heimans JJ, Aaronson NK, et al. Effect of radiotherapy and other treatment-related factors on mid-term to long-term cognitive sequelae in low-grade gliomas: a comparative study. Lancet. 2002;360:1361-1368.
doi.org/10.3171/2019.2.JNS183408, accessed May 17, 2019.
Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
45. DeAngelis LM, Delattre JY, Posner JB. Radiationinduced dementia in patients cured of brain metastases. Neurology. 1989;39:789-796.
Received 19 May 2019; accepted 20 June 2019
46. Douw L, Klein M, Fagel SS, et al. Cognitive and radiological effects of radiotherapy in patients with low-grade glioma: long-term follow-up. Lancet Neurol. 2009;8:810-818.
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47. Rossi M, Ambrogi F, Gay L, et al. Is supratotal resection achievable in low-grade gliomas? Feasibility, putative factors, safety, and functional outcome [e-pub ahead of print]. J Neurosurg. https://
Citation: World Neurosurg. (2019) 131:364-370. https://doi.org/10.1016/j.wneu.2019.06.177
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WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.06.177
Innovation in Neurosurgery: The Concept of Cognitive Mapping Marco Rossi1, Marco Conti Nibali1, Fabio Torregrossa2, Lorenzo Bello1, Giovanni Grasso2
In recent years, advances in cortical-subcortical mapping, intraoperative neurophysiology, and neuropsychology have increased the ability to remove intrinsic brain tumors, expanding indications and maximizing the extent of resection. This has provided a significant improvement in progression-free survival, time of malignant transformation (in low-grade gliomas), and overall survival. Although current techniques enable preservation of language and motor functions during surgery, the maintenance of a complex set of functions defined with the term cognition is not always achievable. Cognition is defined as every neural process underlying a high human function and includes motor haptic and visuospatial functions, memory, social interactions, empathy, and emotions. In this regard, an extensive preoperative and postoperative neuropsychological evaluation is strongly suggested to assess cognitive impairment due to tumor growth, to assess surgical result, and to plan cognitive rehabilitation. This article discusses the main recent innovations introduced for cognitive mapping with the aim to preserve cognitive functions, which are essential to maintain a high quality of life.
INTRODUCTION
M
odern neurosurgical oncology has the goal of maximal tumor resection while at the same time maintaining the patient’ functional integrity, which ultimately defines the so-called onco-functional balance. This has been feasible at the time of surgery by the use of brain mapping techniques, comprehensive use of intraoperative neurophysiology and
neuropsychology.1-3 The surgeon initially performs cortical mapping, to locate functional cortical sites to be spared and to identify negative cortical sites, where to start with the resection. At the subcortical level, the resection is continued while brain mapping is performed until functional boundaries are encountered at the tumor periphery, where tumor removal is stopped. Traditionally, brain mapping has been restricted to pure motor or language functions.4 In the awake or asleep setting, according to the clinical needs, surgeons ask the patient to perform a series of language tasks, while the use of intraoperative neurophysiologic stimulation is locating the sites where interferences are evoked; similarly, overt or electromyography-detected movements can be elicited by the use of direct cortical or subcortical stimulation. However, besides language or pure motor evaluation, full functional preservation requires the maintenance of a complex setup of functions, which are collected under the term of cognition.5 Cognition comprises every neural process that subserves a high human function and includes motor haptic and visuospatial functions, memory, social interactions, empathy, and emotions. In recent years, advances the development in surgical techniques and in the knowledge of brain functional organization have progressively increased surgeons’ ability to remove intrinsic brain tumors, expanding indications and improving the extent of resection. This has been associated with increases in progressionfree survival, malignant transformation time (in low-grade gliomas [LGGs]), and ultimately overall survival.2,3,6-10 Occurring in parallel with these increases, more attention has been increasingly paid to preserve higher cognitive function with the aim of preserving full patient functional integrity and particularly to maintain their quality of life. In fact, although language and motor functions have been mapped and preserved during surgery, many patients reported after surgery the onset of a wide spectrum of cognitive impairments, which ultimately affected their ability to perform routine daily life activities and especially demanding work activities.11 This situation reflects the pioneer status of work in the
Key words Cognition - Eloquent areas - Glioma surgery - Neuropsychological tests
From the 1Neurosurgical Oncology Unit, Department of Oncology and Hemato-Oncology, Università degli Studi di Milano and Humanitas Research Hospital, Istituto di Ricerca e Cura a Carattere Scientifico, Milan; and 2Neurosurgical Clinic, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, Palermo, Italy
Abbreviations and Acronyms DES: Direct electrical stimulation fMRI: Functional magnetic resonance imaging LGG: Low-grade glioma
Citation: World Neurosurg. (2019) 131:364-370. https://doi.org/10.1016/j.wneu.2019.06.177
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To whom correspondence should be addressed: Marco Rossi, M.D. [E-mail: [email protected]]
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field of brain mapping, as it has been reported in a recent systematic review of brain mapping literature that the number of scientific articles focused on mapping and monitoring of functions different from language or motor is still quite limited.4 Of 232 studies analyzed, 207 were mainly focused on language mapping, and <20 evaluated other cognitive domains. A key point of an innovative approach to functional neurosurgery is the adoption of extensive neuropsychological testing in the preoperative evaluation of patients and in their postoperative follow-up. Most deficits related to high cognitive function impairment are quite subtle and usually are not detected during standard neurologic examination and are rarely described clearly by patients or relatives. From this basis, it is recommended to administer before surgery an extensive battery of neuropsychological tests capable of covering all cognitive domains (language, visuospatial abilities, executive function, praxis, fluid intelligence) to detect any preoperative disturbances induced by the growing tumor that are usually undetected by standard testing. The same battery of tests should be administered after surgery and during follow-up to evaluate not only the functional results of surgery but also the impact of cognitive rehabilitation, with the aim of developing and implementing possible strategies to compensate for permanent cognitive deficits.12,13 Despite the need to maximize functional preservation during surgery, the increase in the number of intraoperative tests requested to expand the number of functions to be mapped and preserved may result in an increase in the mapping time requested during the surgical intervention. Although awake procedures are usually well tolerated by patients,14 it is also well known from routine clinical practice that patients’ cooperation usually dramatically decreases with the increase in the surgical and mapping time and with the level of difficulties of the administered test. Hence, it is mandatory to carefully
Figure 1. Intraoperative tasks recommended for performing cognitive or advanced motor mapping. The tasks have been grouped according to the lobe in which they are usually applied and represented on a
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select the intraoperative tasks to be performed according to the site of the tumor having in the mind the type of networks possibly affected or being encountered during the various phases of the resection, tailoring the mapping based on the results of preoperative neuropsychological evaluation and the specific needs of patients. In fact, the best results are obtained when an approach tailored to the individual patient is used. As a consequence, it could be advisable to start the surgery with a core set of basic tests to be performed as soon as possible during the awake phase, with a second set of advanced tests to be performed if the patient is still fully cooperative after the first set. The second set of tests should be selected according to the possible functional networks encountered and taking into consideration specific expectations of individual patients. In this article, we discuss some of the recent innovations introduced during motor and cognitive mapping that have produced a significant improvement in the global functional profile of patients at individual levels. Most of the investigations and tasks described are fully available in the literature and can be considered as ready to be used (Figure 1). INNOVATION IN MOTOR MAPPING Haptic Control Along with language, motor function is probably the main neurologic function to be preserved during neurosurgical procedures. Motor output during stimulation of primary motor area and descending motor pathways has been described since the first surgical procedures performed in awake surgery. In past years, 2 main stimulation techniques, low-frequency stimulation and high-frequency stimulation,1 were introduced and developed to identify the primary motor cortex and the corticospinal tract. Both techniques are widely diffuse and are very effective in
three-dimensional reconstruction of a brain template. Citations of references for each task are provided. RME, Reading the Mind in the Eyes test; PPT, Pyramids and Palm Trees test.
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preserving basic motor function, with a reported rate of permanent postoperative deficit of <5% in most series.15,16 Despite the low rate of permanent motor deficits, particularly in cases where a supratotal resection was achieved, additional motor deficits were detected when a more detailed motor function assessment was performed. A large number of patients treated for lesions located within 2 cm of the central sulcus (either anteriorly or posteriorly) experienced hand apraxia after surgery, despite preserved motor function. Apraxia is the disturbance in timing, sequencing, and spatial organization of movements that render a patient unable to perform daily activities and to return to work at his or her previous level. Rossi et al.17 recently proposed a new intraoperative test based on a tool (called the screwdriver) capable of investigating haptic control of hand movements during surgical procedures for tumor removal. The application of this intraoperative test during awake surgery has been reported to dramatically decrease the prevalence of hand apraxia after surgery, improving patients’ quality of life as well as facilitating their return to work.
Figure 2. Representative case of a patient with a right frontal low-grade glioma who underwent surgery according to functional boundaries in whom advanced motor (haptic) and cognitive mapping was applied at cortical and subcortical levels to guide tumor removal and define subcortically the margins of resection. (A) Preoperative fluid attenuated inversion recovery images (axial, sagittal, and coronal) show a hyperintense lesion in the right frontal lobe, involving the superior and middle frontal gyrus, just anteriorly to the precentral gyrus. Surgery was performed under
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During the test, the patient is invited to perform a rotational movement with the screwdriver tool, while the surgeon by means of direct electrical stimulation (DES) investigates various brain sites at cortical and subcortical levels to identify the sites involved in haptic control. When an arrest of the movement or an alteration of the pattern of the ongoing movement is reported by a neuropsychologist, the site is defined as eloquent for haptic control and preserved during resection. Thanks to this approach, cortical and subcortical networks involved in precise motor control, the so-called praxis network, can be identified and preserved, avoiding the development of hand apraxia in the postoperative period (Figure 2). Administration of the test increases the surgical time of brain mapping by an average of only 12 minutes and does not change the extent of resection. This last point can be explained by the fact that the sites involved in the praxis network are quite discrete, and their preservation, although of functional relevance, does not change on average the degree of surgical resection.17 Besides the relevant clinical impact previously described, this new tool is able to give new insights in the role of nonprimary
asleep-awake-asleep anesthesia with neurophysiologic and neuropsychological mapping and monitoring. (B) The screwdriver test was applied to define the praxis network, which represented the posterior boundary of the resection. The Stroop test was applied to identify the corticostriatal frontal network and represented the inferior margin of the resection. Intraoperative sites of interference recorded for each test are reported and overlapped in the postoperative T1 postgadolinium scan (axial, sagittal, and coronal).
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motor areas in motor control. It also improves knowledge of the functional organization of the hand-knob region at the cortical and subcortical levels. Vigano et al.,18 analyzing the intraoperative neurophysiologic data registered during surgery while the patient was performing the haptic test, showed a rostrocaudal gradient of cortical excitability and different motor interferences during the execution of the task depending on the sites of stimulation. These physiologic data along with tractography reconstruction of the subcortical connectivity (particularly at the level of U-fibers) in the hand-knob area suggest the existence of different connection patterns in relation to the type of interference observed. These data may further expand knowledge of the functional organization of this area and suggest the development of further intraoperative investigational tools to assess it properly. Negative Motor Areas The role of some of the so-called nonprimary areas in the modulation of motor functions has been described by Duffau’s group.19 These investigators described cortical and subcortical sites located mainly in the anterior parietal lobe, which when stimulated by means of DES cause inhibition of voluntary movement. They located these negative motor responses in the postcentral gyrus and in the white matter located deep to the supramarginal gyrus and described a frontoparietal network as the main structure involved in modulating motor control. Furthermore, Rech et al.20 provided the first probabilistic map of negative motor areas of the upper limb and face processing data of 117 patients who underwent awake surgery for diffuse LGG. According to the above-mentioned study, negative motor areas are not randomly distributed, as previously suggested,21 because they are structured cortically along the dorsal and ventral premotor cortex.20 The preservation of such sites was associated with the maintenance of full motor control. In a recent study, Desmurget et al.22 confirmed and further analyzed the phenomenon of negative motor sites in the parietal lobe. The authors described in 16 patients several cortical sites located in the inferior and superior parietal lobule that when simulated by DES during awake surgery caused an inhibition of ongoing voluntary movement without any conscious feeling by the patients. They also reported the electromyographic analysis of the negative motor responses, showing different patterns of motor interference. The clinical significance of such sites is still a matter of investigation. INNOVATION IN COGNITIVE MAPPING Executive Functions Executive functions are a set of supramodal abilities involved in controlling cognitive processes and modulating behavioral changes that take place when someone wants to reach specific goals.23 The executive functions have an important role in everyday activities, such as focusing on a specific task, as well as work activities or social interactions. An impairment in this cognitive domain following a tumor resection has a negative impact on quality of life, as reported by many patients, despite intact neurologic and basic neuropsychological examinations. The neural networks involved in these complex functions are less known compared with the network subserving language
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production and comprehension. Most of the data come from functional magnetic resonance imaging (fMRI) or other functional imaging studies, suggesting a bilateral organization of the networks, mainly involving the frontocorticostriatal region, connecting prefrontal cortices and the basal ganglia.24-26 However, the full anatomic description of this cortical-subcortical network is still not completely available. This lack of knowledge may be one of the reasons why the use of intraoperative mapping and monitoring of higher cognitive function is not prevalent in the operating room. In addition, most of the tests available in the neuropsychological armamentarium are too long or too difficult and not suitable for intraoperative administration. Puglisi et al.23 recently reported an effective intraoperative test designed to map executive functions. In their article, the authors described a simplified version of the Stroop test,27,28 a well-known neuropsychological test used to assess interferences with executive functions, which can be easily administered intraoperatively in awake conditions. They demonstrated the efficacy of the test in detecting subcortical sites in the nondominant frontal lobe, which when spared during surgery preserved the executive functions (Figure 2). Starting from this evidence, further investigation suggested the involvement of the corticostriatal network connecting prefrontal cortices and basal ganglia in subserving such complex functions.23 Mentalization In recent decades, increasing attention has been focused on the preservation of social abilities in patients undergoing resection of intra-axial brain tumors to fully preserve their quality of life. Patients with LGGs are mostly young and after gross total resection or even supratotal resection may have a very long life expectancy. In this specific setting, the preservation of patients’ abilities to communicate and develop normal interactions and build relationships with other people and to continue their previous roles in their families is of significant importance. Social abilities are a complex set of skills, and social neuroscience describes mentalization as one of the key components involved in the ability to interact with others by understanding their mental state.29 An intraoperative adaptation of the neuropsychological test Reading the Mind in the Eye has been developed for intraoperative use during awake procedures. When applied intraoperatively during surgical removal for intrinsic brain tumors, with the aid of DES, the test allowed the surgeon to identify various sites in the nondominant frontal lobe at both cortical and subcortical levels that when spared from resection were associated with the maintenance of mentalization abilities.30 The initial report on the use of this test at the cortical level suggested involvement of the nondominant inferior frontal cortex (pars triangularis and pars opercularis).29 A further report on the use of the intraoperative test at the subcortical level indicated the right arcuate fasciculus as one of the main circuits possibly involved in mediating this complex mental process.31 Starting from the data acquired during intraoperative mentalization testing, Yordanova et al.32 depicted the involvement of a larger network applying task-based fMRI and resting-state fMRI. The intraoperative results of the study confirmed the key role of the right inferior and middle frontal gyrus, whereas resting-state fMRI suggested also the involvement
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of the contralateral frontal lobe and the right posterior temporal gyrus and right inferior parietal lobule. Preservation of this largescale neural network in the right hemisphere should avoid social cognition disorders in the postoperative period, preserving social abilities of patients and ensuring the maintenance of full quality of life. Semantic Association Traditionally, language mapping is performed while the patient is counting or naming. However, language is not restricted to these 2 basic components. The term semantic association refers to the ability to associate similar items together, which is one of the crucial modalities of human language. This component of human language has been described to be mediated by the left ventral stream, mainly the inferior-fronto-occipital fasciculus. The implementation of such a test increased the efficacy of the mapping and patients’ performances after surgery.33 However, semantic processing of information also includes a nonverbal modality. In the past, the anatomo-functional network subserving nonverbal processing functions was not fully identified; a few studies based on fMRI data showed a bilateral activation during execution of a test based on pictures.34 When applying the Pyramids and Palm Trees test, a well-described visual nonverbal semantic association test used in neuropsychological examinations,35 during surgical removal of right hemisphere tumors performed under awake conditions, Herbet et al.33 described interferences in semantic processing due to stimulation of the right inferior fronto-occipital fasciculus. Despite this encouraging evidence of the role of the right inferior fronto-occipital fasciculus in nonverbal semantic processing, the clinical impact of the preservation of the sites giving interferences during stimulation while the patient was performing this task is not fully known, and more work needs to be done in this direction. Visuospatial Abilities Visuospatial abilities include all the mental skills needed to identify and analyze a space and to interact with it. The most relevant clinical manifestation of deficits in visuospatial abilities is spatial neglect, a clinical condition in which the patient, in the absence of visual field or sensorimotor deficit, is unable to explore space contralateral to the affected side. Spatial neglect was described first in stroke literature as a result of parietal stroke. In recent decades, attention has also been given to visuospatial abilities in patients undergoing surgery for resection of parietal lobe tumors. Initially, a test called line bisection was proposed,36 but more recently another neuropsychological test adapted for the intraoperative setting has been published, the target cancellation task, with similar results.37 In the target cancellation task, distinct simple shapes are shown to patients on a handheld touchscreen tablet with a vertical line dividing the screen into 2 equal halves. Patients are trained beforehand to cancel with a swiping movement of a finger the specifically targeted shape in both the right and the left fields. The main constraint of the administration of these tests is related to their repeatability, particularly because the test is generally administered when the patient is lying in a lateral position.
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ADJUNCT FACTORS ASSOCIATED WITH COGNITION IMPAIRMENT It has been pointed out that besides preoperative and postoperative evaluation, tumor-related factors can affect cognitive dysfunction in patients with gliomas, particularly LGGs. The tumor itself adversely affects neurobehavioral function in patients with LGGs.38 Tumor localization seems to be one of the most important factors. In this regard, tumors located in the dominant temporal or frontal area usually affect language function owing to the organization of linguistic function.39 Accordingly, neoplastic lesions infiltrating the uncinate fasciculus39,40 provide a higher grade of language impairment than tumors located near the arcuate fasciculus.41 In this regard, radiotherapy has been shown to strongly affect the quality of life of patients through deleterious effects on brain parenchyma resulting in cognitive deficits and dementia.42,43 In this regard, several differences in mean cognitive function scores between patients with LGGs who received radiotherapy and patients who did not have been reported.44 Variables such as overall dose and treatment volume and the size of the fraction dose have been largely identified as responsible factors for the development of late neurotoxicity.45 In particular, radiotherapy given in daily fractions >2 Gy has been shown to be harmful for the normal surrounding brain over time, in contrast to conventional external-beam radiotherapy. A subsequent study investigating radiologic and cognitive sequelae in patients with LGGs at a mean follow-up of 12 years after radiotherapy showed a progressive decline in attentional functioning, including patients who received fraction doses regarded as safe (2 Gy).46 These cognitive deficits were also associated with radiologic abnormalities.46 Based on the evidence that radiotherapy affects cognitive function, including in the long run, the use of this therapeutic strategy in LGG should be delayed as much as tumor progression allows and tempered with the progression of the tumor. Finally, clinical evidence suggests that medical treatments can affect cognitive function. For instance, the use of antiepileptics has been associated with poorer objectively measured and selfreported cognitive function compared with patients in whom antiepileptics were not used.44 However, this issue requires further investigation before a firm conclusion can be established. CONCLUSIONS Recent advances in surgical techniques have expanded the indications for and increased the extent of resection of intrinsic brain tumors, producing a significant improvement in progression-free survival, time of malignant transformation (in low-grade gliomas), and overall survival. This significant change in the natural history of intrinsic brain tumors has occurred in parallel with the need to increase patients’ full functional integrity. Patients are surviving longer in good clinical condition, but at the same time are experiencing the onset of functional disturbances in addition to the traditionally considered basic motor or language functions. This situation has led to the need to develop additional tests to explore more complex cognitive functions and to develop intraoperative tasks able to identify cortical or subcortical sites possibly involved in these functions.
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The main constraint of this pioneering work is the need to develop tests that are easily administered in the intraoperative setting and are effective in investigating the function for which they were designed. In this article, we described innovative tests that when applied during surgery in awake conditions were able to detect a
REFERENCES 1. Rossi M, Sani S, Nibali MC, Fornia L, Bello L, Byrne RW. Mapping in low-grade glioma surgery: low- and high-frequency stimulation. Neurosurg Clin N Am. 2019;30:55-63. 2. De Witt Hamer PC, Robles SG, Zwinderman AH, Duffau H, Berger MS. Impact of intraoperative stimulation brain mapping on glioma surgery outcome: a meta-analysis. J Clin Oncol. 2012;30: 2559-2565. 3. Duffau H, Taillandier L. New concepts in the management of diffuse low-grade glioma: proposal of a multistage and individualized therapeutic approach. Neuro Oncol. 2015;17:332-342. 4. Ruis C. Monitoring cognition during awake brain surgery in adults: a systematic review. J Clin Exp Neuropsychol. 2018;40:1081-1104. 5. Duffau H. Preserving quality of life is not incompatible with increasing overall survival in diffuse low-grade glioma patients. Acta Neurochir (Wien). 2015;157:165-167. 6. Duffau H. Long-term outcomes after supratotal resection of diffuse low-grade gliomas: a consecutive series with 11-year follow-up. Acta Neurochir (Wien). 2016;158:51-58. 7. Smith JS, Chang EF, Lamborn KR, et al. Role of extent of resection in the long-term outcome of low-grade hemispheric gliomas. J Clin Oncol. 2008; 26:1338-1345. 8. Buckner J, Giannini C, Eckel-Passow J, et al. Management of diffuse low-grade gliomas in adults—use of molecular diagnostics. Nat Rev Neurol. 2017;13:340-351. 9. Grasso G. Extent of resection and survival in glioblastoma multiforme. JAMA Oncol. 2016;2: 1508-1509. 10. Grasso G, Torregrossa F, Leone L. Maximizing the extent of resection in high-grade glioma. World Neurosurg. 2019;123:256-258. 11. Mandonnet E, Sarubbo S, Duffau H. Proposal of an optimized strategy for intraoperative testing of speech and language during awake mapping. Neurosurg Rev. 2017;40:29-35.
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series of functions involved in the maintenance of various cognitive domains. When a functional approach is applied, large resections outside tumor borders are feasible without any additional neurologic or neuropsychological deficit in a large percentage of patients.47
Low Grade Glioma Network multicenter study. Acta Neurochir (Wien). 2013;155:1301-1308. 15. Bello L, Riva M, Fava E, et al. Tailoring neurophysiological strategies with clinical context enhances resection and safety and expands indications in gliomas involving motor pathways. Neuro Oncol. 2014;16:1110-1128. 16. Han SJ, Morshed RA, Troncon I, et al. Subcortical stimulation mapping of descending motor pathways for perirolandic gliomas: assessment of morbidity and functional outcome in 702 cases [e-pub ahead of print]. J Neurosurg. https://doi.org/ 10.3171/2018.3.JNS172494, accessed August 1, 2018. 17. Rossi M, Fornia L, Puglisi G, et al. Assessment of the praxis circuit in glioma surgery to reduce the incidence of postoperative and long-term apraxia: a new intraoperative test. J Neurosurg. 2018;130: 17-27. 18. Vigano L, Fornia L, Rossi M, et al. Anatomofunctional characterisation of the human “handknob”: a direct electrophysiological study. Cortex. 2019;113:239-254. 19. Almairac F, Herbet G, Moritz-Gasser S, Duffau H. Parietal network underlying movement control: disturbances during subcortical electrostimulation. Neurosurg Rev. 2014;37:513-516 [discussion: 516-517]. 20. Rech F, Herbet G, Gaudeau Y, et al. A probabilistic map of negative motor areas of the upper limb and face: a brain stimulation study. Brain. 2019;142:952-965. 21. Borggraefe I, Catarino CB, Remi J, et al. Lateralization of cortical negative motor areas. Clin Neurophysiol. 2016;127:3314-3321. 22. Desmurget M, Richard N, Beuriat PA, et al. Selective inhibition of volitional hand movements after stimulation of the dorsoposterior parietal cortex in humans. Curr Biol. 2018;28:3303-3309.e3. 23. Puglisi G, Sciortino T, Rossi M, et al. Preserving executive functions in nondominant frontal lobe glioma surgery: an intraoperative tool [e-pub ahead of print]. J Neurosurg. https://doi.org/10. 3171/2018.4.JNS18393, accessed September 1, 2018.
12. Duffau H. A new philosophy in surgery for diffuse low-grade glioma (DLGG): oncological and functional outcomes. Neurochirurgie. 2013;59:2-8.
24. Langen M, Leemans A, Johnston P, et al. Frontostriatal circuitry and inhibitory control in autism: findings from diffusion tensor imaging tractography. Cortex. 2012;48:183-193.
13. Duffau H, Mandonnet E. The “onco-functional balance” in surgery for diffuse low-grade glioma: integrating the extent of resection with quality of life. Acta Neurochir (Wien). 2013;155:951-957.
25. Fedorenko E, Duncan J, Kanwisher N. Broad domain generality in focal regions of frontal and parietal cortex. Proc Natl Acad Sci U S A. 2013;110: 16616-16621.
14. Beez T, Boge K, Wager M, et al. Tolerance of awake surgery for glioma: a prospective European
26. Lipszyc J, Levin H, Hanten G, Hunter J, Dennis M, Schachar R. Frontal white matter damage impairs
WORLD NEUROSURGERY 131: 364-370, NOVEMBER 2019
response inhibition in children following traumatic brain injury. Arch Clin Neuropsychol. 2014;29: 289-299. 27. Stuss DT, Floden D, Alexander MP, Levine B, Katz D. Stroop performance in focal lesion patients: dissociation of processes and frontal lobe lesion location. Neuropsychologia. 2001;39:771-786. 28. MacLeod CM. Half a century of research on the Stroop effect: an integrative review. Psychol Bull. 1991;109:163-203. 29. Herbet G, Lafargue G, Moritz-Gasser S, Bonnetblanc F, Duffau H. Interfering with the neural activity of mirror-related frontal areas impairs mentalistic inferences. Brain Struct Funct. 2015;220:2159-2169. 30. Herbet G, Lafargue G, Bonnetblanc F, et al. Inferring a dual-stream model of mentalizing from associative white matter fibres disconnection. Brain. 2014;137:944-959. 31. Nakajima R, Yordanova YN, Duffau H, Herbet G. Neuropsychological evidence for the crucial role of the right arcuate fasciculus in the face-based mentalizing network: a disconnection analysis. Neuropsychologia. 2018;115:179-187. 32. Yordanova YN, Cochereau J, Duffau H, Herbet G. Combining resting state functional MRI with intraoperative cortical stimulation to map the mentalizing network. Neuroimage. 2019;186: 628-636. 33. Herbet G, Moritz-Gasser S, Duffau H. Direct evidence for the contributive role of the right inferior fronto-occipital fasciculus in non-verbal semantic cognition. Brain Struct Funct. 2017;222:1597-1610. 34. Rice GE, Lambon Ralph MA, Hoffman P. The roles of left versus right anterior temporal lobes in conceptual knowledge: an ALE meta-analysis of 97 functional neuroimaging studies. Cereb Cortex. 2015;25:4374-4391. 35. Howard D, Patterson KE. The Pyramids and Palm Trees Test: A Test for Semantic Access from Words and Pictures. Bury St. Edmunds, UK: Thames Valley Test Company; 1992. 36. Vallar G, Bello L, Bricolo E, et al. Cerebral correlates of visuospatial neglect: a direct cerebral stimulation study. Hum Brain Mapp. 2014;35: 1334-1350. 37. Conner AK, Glenn C, Burks JD, et al. The use of the target cancellation task to identify eloquent visuospatial regions in awake craniotomies: technical note. Cureus. 2016;8:e883. 38. Taphoorn MJ, Schiphorst AK, Snoek FJ, et al. Cognitive functions and quality of life in patients with low-grade gliomas: the impact of radiotherapy. Ann Neurol. 1994;36:48-54.
www.journals.elsevier.com/world-neurosurgery
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39. Naidich TP, Hof PR, Gannon PJ, Yousry TA, Yousry I. Anatomic substrates of language: emphasizing speech. Neuroimaging Clin N Am. 2001; 11:305-341. 40. Papagno C, Miracapillo C, Casarotti A, et al. What is the role of the uncinate fasciculus? Surgical removal and proper name retrieval. Brain. 2011; 134:405-414. 41. Zhao Y, Chen X, Wang F, et al. Integration of diffusion tensor-based arcuate fasciculus fibre navigation and intraoperative MRI into glioma surgery. J Clin Neurosci. 2012;19:255-261. 42. Crossen JR, Garwood D, Glatstein E, Neuwelt EA. Neurobehavioral sequelae of cranial irradiation in adults: a review of radiation-induced encephalopathy. J Clin Oncol. 1994;12:627-642. 43. Surma-aho O, Niemela M, Vilkki J, et al. Adverse long-term effects of brain radiotherapy in adult
370
www.SCIENCEDIRECT.com
IN
NEUROSURGERY SPECIAL SECTION
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low-grade glioma patients. Neurology. 2001;56: 1285-1290. 44. Klein M, Heimans JJ, Aaronson NK, et al. Effect of radiotherapy and other treatment-related factors on mid-term to long-term cognitive sequelae in low-grade gliomas: a comparative study. Lancet. 2002;360:1361-1368.
doi.org/10.3171/2019.2.JNS183408, accessed May 17, 2019.
Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
45. DeAngelis LM, Delattre JY, Posner JB. Radiationinduced dementia in patients cured of brain metastases. Neurology. 1989;39:789-796.
Received 19 May 2019; accepted 20 June 2019
46. Douw L, Klein M, Fagel SS, et al. Cognitive and radiological effects of radiotherapy in patients with low-grade glioma: long-term follow-up. Lancet Neurol. 2009;8:810-818.
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47. Rossi M, Ambrogi F, Gay L, et al. Is supratotal resection achievable in low-grade gliomas? Feasibility, putative factors, safety, and functional outcome [e-pub ahead of print]. J Neurosurg. https://
Citation: World Neurosurg. (2019) 131:364-370. https://doi.org/10.1016/j.wneu.2019.06.177
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