Key Message: Awake mapping should be considered using appropriate and customized testing paradigms during resection of dominant SMA gliomas. The frontal lobe (FL) is the most common site of occurrence of adult diffuse gliomas.[1] On the lateral surface, it broadly consists of the primary motor area (M1), the premotor region (dorsal and ventral), and the prefrontal cortex (PFC). The dorsal premotor cortex is located in the superior and middle frontal gyri. Histologically, the agranular area located in the medial frontal lobe rostral to the primary motor area (M1) is identified as the supplementary motor area (SMA), which is further divided into SMA proper and pre-SMA. These areas are involved in planning and smooth execution of complex motor functions and via relays from the dorsal language stream modulate speech generation and phonological processing,[2] respectively. Lesions involving the SFG pose a specific challenge due to partial or complete involvement of pre-SMA and SMA regions as well as the subcortical networks. Though widely thought to be reversible, the classical SMA syndrome, as originally described by Laplane, clearly described persistent deficits in motor dexterity and bimanual complex movements, besides speech initiation.[3] If these functions are to be preserved, awake mapping of motor cognition and speech is mandatory. Objective In this article, we demonstrate the technique of resecting a dominant superior frontal gyrus tumor involving the pre-SMA and SMA region under awake conditions with DES emphasizing the need to consider awake mapping to prevent prolonged/permanent language and motor deficits. Clinical Presentation A 40-year-old male, right-handed engineer came with a history of two episodes of generalized tonic clonic seizures approximately 2 months back, which was controlled by a single antiepileptic agent with no breakthrough seizures. Magnetic resonance imaging (MRI) brain [Figure 1] showed a T2 hyperintense, T1 isointense, non-contrast enhancing, diffuse infiltrative intra-axial mass involving the left superior frontal gyrus and the dominant SMA. Further evaluation with functional MRI (fMRI) showed BOLD signal activation on covert speech task abutting the posteroinferior margin of the tumor representing vPMC (ventral premotor cortex) and DTI (diffusion tensor imaging) showing frontal aslant tract (FAT) and corticospinal tract (CST) abutting the posterior surface of the tumor [Figure 1].Figure 1: Pre-operative multi-planar MRI scans; T2 WI (a): axial section, (b): coronal section, and (c): sagittal section showing a diffuse infiltrative heterogeneously hyperintense lesion in left superior frontal gyrus. (d): No post-gadolinium enhancement. (e): fMRI showing BOLD signal activation of vPMC abutting the posterior border of tumor. (f): 3D-segmented DTI showing the fronto-aslant tract FAT (Pink) and CST (Blue) abutting the posterior border of tumorSurgery: Left frontoparietal awake craniotomy and resection of superior frontal gyrus glioma under intra-operative neuromonitoring and navigated ultrasound guidance. Equipment used: Navigated ultrasound system: Brainlab KICK navigation with ultrasound navigation software (BRAINLAB AG, Munich, Germany) coupled with a high-end cranial ultrasound machine (bk5000®; BK Medical, Denmark) using an N13C5 navigated curvilinear probe. Mapping and monitoring: NimEclipse (version 4.2.422) (Medtronics Inc., Minneapolis. MN, USA) with a bipolar 50-Hz cortical stimulator, a monopolar stimulator (train-of-five pulses), and cortical strip motor evoked potentials (MEPs). Anesthesia: Scalp block and initial sedation (dexmedetomidine) with laryngeal mask airway (LMA). Position: Right lateral, neck neutral, head fixed on the Mayfield three pin fixation system, and pressure points well padded. Incision: Left fronto-parieto-temporal question mark incision. Steps of Surgery Comfortable lateral position on a horse shoe Starting sedation and LMA insertion Pin site block followed by placement of head pins Navigation registration and marking incision Complete local scalp block followed by painting and draping (this is done after the navigation registration to avoid inaccuracies in surface matching that may arise when the anesthetic is infiltrated in the scalp) Frontotemporal craniotomy (wide exposure) Pre-durotomy 3D navigated intra-operative ultrasound (3D NUS) to delineate the tumor extent Awakening the patient and removing LMA at durotomy. 10–20 min for the patient to be fully cooperative for neuropsychological tests Cortical mapping with DES using specific tests (number counting, spontaneous motor twitches and active motor task, picture naming) to identify the functional boundaries Circumferential pial coagulation and subpial dissection of tumor bearing gyrus Subcortical mapping to identify and preserve the white matter networks of the SMA (tests as above) Completion of resection and enmass removal of the specimen Resection control 3DNUS to confirm the resection status. Video Link https://youtu.be/PJWljVA3msU QR Code: Video Timeline With Audio Transcript 00:00 to 00:19: In this video, we would like to describe the principles of surgery as well as the technical aspects of awake craniotomy and mapping for a diffuse low-grade glioma of the dominant superior frontal gyrus located close to the premotor cortex and underlying subcortical networks, emphasizing the role of awake mapping and monitoring. 00:20 to 00:55: This was a young engineer, right-handed, who presented with seizures and no neurological deficits, and on neurocognitive assessment, he only had mild semantic fluency affected. MRI multi-planar T1, T2 images showed a non-enhancing T2 hyper-intense lesion in the left superior frontal gyrus involving the SMA region. Medially, the tumor involved cingulum reaching up to and indenting the corpus callosum, there was negligible contrast enhancement, suggestive of a diffuse lower-grade glioma, probably IDH mutant. 00:56 to 01:27: It is important to understand that on the dominant side, besides motor integration, the SMA region is also involved and important for speech initiation. Besides cortical networks, the subcortical substrates at risk include the cingulum inferomedially, callosal fibers and the frontal aslant posteroinferiorly along with the corticospinal tract, and the SLF-arcuate terminations in the middle frontal gyrus laterally. The IFOF itself is relatively far away. 01:28 to 02:15: This patient was taken up for the awake craniotomy and asleep–awake technique. Tumor extent is evident in the superior frontal gyrus outline. Cortical mapping commenced with identifying the primary motor area using monopolar mapping. Then bipolar stimulation was used for establishing the threshold for further mapping. First, anarthia was elicited (not shown here), and using the same threshold of 2 milliamps, the negative motor phenomenon of stoppage of movement of the upper limb was mapped just posterior to the tumor boundary. At the same threshold with picture naming, there was speech delay seen at the dorsolateral prefrontal cortex, which is the termination of the IFOF. Thus, the functional cortical margins were outlined. 02:16 to 03:06: Once done, subpial circumferential dissection was commenced of the entire tumor-bearing gyrus, simultaneously monitoring the patient for motor and speech functions. General principles of subpial dissection ensure a complete gyral resection. The controlled ultrasonic aspirator is a very useful tool to prevent pial injury. At the white matter level, functional mapping is essential. In this case, associative motor speech areas of the pre-SMA fronto-aslant fibers and the motor execution networks, the frontostriatal fibers, were encountered on bipolar mapping, marking the limits of subcortical resection posteriorly and laterally, where a thin layer of tumor was left behind to avoid permanent deficits in dexterity and motor movement. 03:07 to 04:35: Circumferential resection was carried out all around with constant monitoring of the patient as described earlier. Medially, the superior frontal gyrus and the anterior cingulate were resected subpially, carefully preserving the distal branches of the anterior cerebral artery complex. In the awake patient, sometimes, this may elicit pain, and therefore, this step can be optionally done once the patient is put asleep at the end of surgery. En-block removal is completed, leaving a small nubbin behind at the base, overlying the eloquent white matter. Then this is gradually removed layer by layer using an ultrasonic aspirator, all the time constantly monitoring the patient. Resection was confirmed using intra-operative ultrasound. The positively mapped subcortical regions were depicted in the cavity here. Proximity of these fibers to the tumor edge reinforced the need to map them under awake conditions. The summary of the mapped regions is diagrammatically represented here. 04:36 to 04:54: Post-operative MRI confirms a near total resection with a thin sliver of tumor posteriorly where the negative motor networks are encountered. Preservation of the networks is confirmed on the post-operative tractography. 04:56 to 06:41: Post-operatively, this patient had no motor deficits; speech and comprehension were intact. However, difficulty in initiation of spontaneous speech and perseveration was noted. Reading and writing were intact. There was perseveration noted and difficulty in initiation of speech. He is not able to answer those questions. However, repetition is preserved. 06:42 to 07:22: The spectrum of normal comprehension, normal repetition, and difficulty in spontaneous motor speech initiation is a classical triad of transcortical motor aphasia seen in pre-SMA regions. In his case, it was transient and recovered over 3 weeks on follow-up. Radical surgeries with positive mapping often lead to transient neurological deficits, especially in the mapped functions. However, these are almost always reversible. This case highlights the rationale behind awake mapping in dominant SMA lesions and outlines the technical principles. Thank you. Outcome Post-operatively, this patient developed a syndrome of transcortical motor aphasia. Post-operative day 1 MR scans revealed expected residue posteriorly as seen on intra-operative NUS [Figure 2]. The patient was started on speech rehabilitation and discharged on POD6. Histopathology revealed IDH R132H mutated diffuse astrocytic tumor (WHO grade 3), and the patient was started on appropriate adjuvant treatment with radiotherapy (59.4 Gy/33#) and concurrent temozolamide. At post-operative 3-month follow-up, the patient had improved almost completely, with mild persistent residual impairment in speech initiation.Figure 2: Post-operative day 1 MRI scans; (a and b): Axial and coronal T2 sequences showing expected posteroinferior residual tumor. (c): Post-operative DTI segmentation showing the posterior extent of resection cavity (white arrow) attenuating the FAT (pink)Pearls and Pitfalls Awake mapping in SMA region tumors should be done meticulously and with appropriate and carefully selected tasks. The tasks should be individualized keeping in mind to map function, both cortically and sub-cortically. Table 1 describes the tests, interpretation of results, and the corresponding substrate tested.Table 1: Tests and tasks commonly used for awake mapping during resection of SMA region tumorsMapping at the sub-cortical region is more important. Negative motor and speech responses are usually encountered rostral to the primary motor responses. Preservation of these networks almost always ensures that the primary motor fibers have been preserved. MEPs to monitor the CSTs can be employed and provide corroboration and complementary information on the integrity of the primary motor networks (but not the negative motor pathways). Following radical functional resections (where mapping yields function at the boundaries of the resection), transient post-operative worsening is the norm. The same must be communicated to the patient prior to surgery. Complete recovery is almost universal. Discussion SMA was first described by Penfield in 1951 as a well-defined cortical area in the expanse of the mesial frontal lobe just anterior to the primary motor foot area, which on stimulation resulted in vocalization and negative motor responses.[4] Based on cyto-architecture, responses on functional imaging, or electrical stimulation, the region is divided into rostral pre-SMA or language SMA and dorsal SMA proper by an imaginary line through AC drawn perpendicular to the AC–PC line.[5] The language SMA/pre-SMA has connections with various networks subserving the dorsal language stream. The SMA proper is proposed to have a topographical representation of fibers from lower limbs, upper limbs, face, and language arranged posterior to anterior.[6] Fontaine et al.[7] in their study have corroborated the presence of SMA somatotopy and showed incremental speech and descending motor deficits with increasing posterior extent of resection in superior frontal gyrus lesions. While dealing with lesions in superior frontal gyrus, not only its relation to the cortical SMA region is important but also its subcortical connections should also be taken into consideration to avoid neuro-deficits that can hamper the patient's quality of life (QOL). One such important sub-cortical fiber network is the FAT (frontal aslant tract), which is an oblique bundle of white matter tract that connects SMA, pre-SMA, and part of SFG superomedially to the pars opercularis and pars triangularis inferolaterally. It has a demonstrated role in speech functions like initiation, modulation, sentence formation, and lexical decisions along with contribution to motor and executive functions, working memory, and social tasks and is thought to be an important substrate in development of speech deficits due to SMA complex insult.[8] Other sub-cortical networks in close proximity are frontostriatal tracts and SLF-II. The frontostriatal tract (FST) is a projection fiber of SMA complex and connects it to the caudate and striatum.[9] This tract is difficult to demonstrate on DTI and is believed to be involved in motor coordination and processing (especially contralateral). In the first description of the SMA syndrome by Laplane et al.,[3] it was typically thought to transiently affect motor function, resulting in a paucity of complex motor movements and volitional speech. But the paper also recorded persistent long-term deficits in bimanual coordination. Recent studies have unearthed more complex attributes of the SMA syndrome and have described cognitive and language deficits along with the pure motor domain of the syndrome.[10] SMA lesions are thought to produce more “speech related dysfunctions” (speech initiation, automatization, and monitoring) as well as task switching difficulties, while insult at the pre-SMA region is associated with development of “language related dysfunctions” like difficulty in prosody, lexical disambiguation, syntax, and context tracing.[11] Affection of left pre-SMA results in language dysfunction in all these domains and results in the syndrome of “transcortical motor aphasia”, which is classically defined as a syndrome of non-fluent verbal output with preserved repetition and comprehension, with or without other non-cardinal deficits like anomia, agrammatism, and paraphasia.[12] Post-operative SMA syndrome complex is traditionally believed to be transient in nature with partial or complete resolution seen in 80% patients in an average duration of 45 days, while persistent prolonged deficits mainly in speech are seen in approximately 20% patients.[13] However, not all reported studies document meticulously mapped sub-cortical SMA networks. When mapped systematically and preserved, the risk of long-term deficits is negligible.[14] The role of awake mapping for language and motor functions for SMA tumor resections has been a matter of debate. Critics suggest that awake mapping may result in early appearance of language or negative motor deficits that may compel the surgeon to resect less due to apprehension of creating a morbid deficit which otherwise is known to be grossly reversible, and these studies argue more in favor of resecting till functional motor boundaries attained by sub-cortical monitoring during resection under anesthesia.[15,16] Noteworthy in all these studies, post-operative detailed neuropsychological evaluation was not done, and thus, subtle deficits in movement kinematics/praxis, language, and cognition due to involvement of pre- SMA networks were not taken cognizance of. Whereas intra-operative deficits do herald a post-operative deficit, when these responses are elicited by meticulous DES using an appropriate task, they reliably provide a functional margin for the extent of resection. Deficits arising after such radical resections are often reversible as mentioned. On the other hand, when such deficits occur (as part of the post-operative SMA syndrome) in surgeries done under GA, it is difficult to predict the reversibility of the deficits. The residual deficits of pre-SMA injury, although not very overt, may affect patients' higher mental function and motor dexterity, which in case of professional individuals may hamper their ability to go back to work. In case of sub-total resections, neuroplasticity can permit functional reorganization of eloquent networks over time, permitting staged resections of tumors, especially lower-grade gliomas.[17] Conclusion Awake mapping should be considered using appropriate and customized testing paradigms during resection of dominant SMA gliomas. All anticipated deficits and their evolution post-operatively as well as short-term and long-term impacts on the patient's work should be discussed in detail upfront, and a decision on acceptance of deficit should be made beforehand. This “a la carte” approach can help decide resective intent pre-operatively, which can result in good patient cooperation intra-operatively and can help achieving maximal safe resection. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.