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Thalamic and Insular Tumors
23
Thalamic and Insular Tumors: Minimizing Deficits SHAWN L. HERVEY-JUMPER, MITCHEL S. BERGER
HIGHLIGHTS • Insular and thalamic intrinsic brain tumors pose perioperative risk due to their proximity to functional cortical and subcortical pathways and neurovascular structures. • Preservation of M2 insular and lenticulostriate arteries is critical to prevent postoperative stroke. • Cortical and subcortical mapping to identify language and motor sites, particularly the posterior limb of the internal capsule, limits the risk of postoperative deficits.
Introduction The role of surgery in the treatment of intrinsic brain tumors is to establish the correct histologic and molecular diagnosis, relieve mass effect, and provide maximal safe resection to improve both overall and progression-free survival. Nearly 50% of tumors are within difficult-to-access areas, with either presumed functional significance or close association with vascular structures. Surgical decisions therefore must balance reduction of tumor volume with avoidance of important neurovascular structures. Gliomas are the most common primary intrinsic brain tumor. The majority of gliomas are located in the cerebral hemispheres; however, 6.4% are located within the deep structures of the cerebrum, including primarily the insula and thalamus.1,2 Tumors within the insula and thalamus remain a challenge to manage given proximity to functionally significant areas and intimate relationship with vascular structures. Surgical techniques such as awake craniotomy with cortical and subcortical mapping permit maximal extent of resection while minimizing postoperative morbidity.3,4 Intraoperative violation of cortical and subcortical functional pathways may lead to immediate neurologic sequelae, negatively impacting quality of life and survival. Additionally, injuries to branches of the middle cerebral artery or lenticulostriate arteries are well reported and often have catastrophic consequences, which can range from (1) stroke to (2) hemorrhage, (3) vasospasm, or (4) thrombosis. This chapter will discuss surgical approaches for intrinsic brain tumors located within the thalamus and insula.
Indications for Surgery Gliomas and brain metastasis are the most common deep-seated intrinsic brain tumors, with the most robust body of literature in support of maximal safe resection. There are four histologic grades 120
for gliomas recognized by the World Health Organization (WHO). Grade I tumors have minimal proliferative potential and circumscribed growth. WHO grade II gliomas include diffuse astrocytoma, pleomorphic xanthoastrocytoma, and oligodendroglioma. These tumors have low mitotic activity; however, given their infiltrative nature, they have a tendency to recur, albeit most commonly near the site of initial presentation. WHO grade III gliomas, such as anaplastic astrocytoma, display nuclear anaplasia and increased cellularity. Glioblastomas are WHO grade IV gliomas and represent the most common primary brain tumor in adults. Numerous studies have examined the relationship between extent of resection and volume of residual tumor, overall survival, progression-free survival, and time to malignant transformation among patients with low- and high-grade gliomas.2,5–26 Although no class I data exist, the majority of published reports suggest that greater extent of resection improves overall survival and progression-free survival, and lengthens the time to malignant transformation.
Anatomic Insights and Surgical Approach Intrinsic brain tumors within the insula or thalamus were previously considered inoperable due to the high risk of perioperative complications. However, a combination of improved microsurgical techniques, neuroanesthesia, and advanced structural and functional imaging permit greater access to many insular and thalamic tumors. Surgical approach and technical considerations for tumors within the insula and thalamus are discussed in this chapter.
Approaches to the Insula Opercular landmarks at the cerebral surface may be beneficial to localize structures within the insula. The insula is a triangular-shaped structure within the sylvian fissure, which lies deep to the frontal, parietal, and temporal lobes. The optimal approach to insular lesions may require either splitting the sylvian fissure or resecting the overlying operculum; therefore it’s critical to know both sylvian fissure anatomy and cortical opercular landmarks. The sylvian fissure consists of a central stem in addition to horizontal, anterior ascending, and posterior rami. The longest portion of the sylvian fissure is the posterior ramus, which extends posterior and superior and terminates in the inferior parietal lobule. The anterior horizontal and anterior ascending rami are shorter and divide the inferior frontal gyrus into the pars opercularis, orbitalis, and triangularis. The insular surface faces laterally and is enclosed by the anterior
CHAPTER 23 Thalamic and Insular Tumors: Minimizing Deficits
and posterior limiting (also known as circular) sulci. The limiting sulcus has anterior, superior, and inferior parts.27 The insular cortex is composed of an anterior limen insula, central sulcus, three anterior short gyri, and two posteriorly placed long gyri. The central sulcus of the insula is a continuation of the central sulcus of the cerebral hemispheres. Two anterior sulci separate the three short gyri, and a single sulcus separates the two long posterior gyri. The insular pole is located at the anteroinferior edge of the insula, where the short gyri converge to form a rounded area lateral to the limen. The insular apex is the highest and most prominent laterally projecting area on the insular convexity. Lying underneath the cortical surface of the pars opercularis is the superior portion of the anterior and middle short insular gyri. Posteriorly, the supramarginal gyrus overlies the superior limiting sulcus and the superior portion of the posterior long gyri. The limen insula overlies the uncinate fasciculus.27,28 Additionally, the anterior perforated substance lies medial to the limen. The middle cerebral artery bifurcates at the limen insula, forming M2 branches, which overlay the insular surface. Insular tumors are among the most challenging neurosurgical lesions to manage. Tumor location and hemisphere of language dominance determine whether a transcortical or transsylvian approach should be considered.28 Patients are put in a semilateral position with the head parallel to the floor.29 For tumors located predominantly above or below the sylvian fissure, the vertex of the head is positioned 15 degrees toward the floor. The craniotomy is tailored based on tumor location and involvement of the overlying frontal or temporal operculum. Insular tumors may be approached based on their location within four zones. The sylvian line divides the insular cortex into dorsal and ventral parts. The foramen of Monro divides the insula into rostral and caudal portions, creating four zones.4 The transcortical exposure offers the maximal insular exposure with the widest surgical window and surgical freedom.28 The insular surface is exposed and surgical resection continues as the vessels of the sylvian fissure are skeletonized, which creates “surgical windows.” The resection is continued by working under the sylvian fissure along the uncinate fasciculus. Cortical and subcortical sensorimotor and language mapping may be utilized, particularly for posterior zone 2 and 3 tumors. The suprasylvian lenticulostriate arteries must be identified and preserved, and subcortical motor mapping of the corticospinal tract marks the medial border of the resection.
Approaches to the Thalamus The choice of surgical approach for thalamic tumor resection balances tumor location, vascularity, and the location of the posterior limb of the internal capsule. Thalamic tumors are relatively rare, representing 2% of all brain tumors.30 Although lesions in this location have historically been surgically treated with stereotactic biopsy alone, advanced structural imaging and microsurgical techniques have allowed for surgical resection with acceptable perioperative morbidity. The surgical corridor of choice uses the shortest route to the tumor avoiding the internal capsule and normal thalamus. These decisions are made based on careful study of preoperative axial and coronal magnetic resonance imaging (MRI) with addition of diffusion tensor imaging (DTI) tractography. Operative approaches include (1) middle temporal gyrus approach, (2) occipital transtentorial approach, (3) middle frontal gyrus approach, (4) transcallosal approach, and (5) combined approaches.30 Surgical resection is reserved for contrast-enhancing tumors with clear margins on preoperative imaging. Nonenhancing tumors
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with poorly defined margins should be treated with biopsy alone given their propensity to have functional tissue within the lesion. Surgical approach is based on tumor location (anterior or posterior within the thalamus) and proximity to the posterior limb of the internal capsule. The middle temporal gyrus approach is used predominantly for posterolateral tumors close to the temporal horn of the lateral ventricle. The occipital transtentorial approach offers maximal exposure for posterior medially placed thalamic tumors in close proximity to the third ventricle. The middle frontal gyrus approach is used for anterolateral thalamic tumors extending superiorly into the frontal lobe. The transcallosal approach is rarely used but is saved for anteromedial thalamic tumors. The majority of deep-seated intrinsic tumors cause anterolateral displacement of the posterior limb of the internal capsule, making the middle temporal gyrus corridor the common approach. After a temporal corticectomy, the tumor is approached through the lateral ventricle along the posterolateral margin of the tumor. Upon reaching the temporal horn of the lateral ventricle, the tumor is approached through the choroidal fissure. This approach ensures an entry corridor inferior to the insula and posterior to the internal capsule.
Complications Surgery for intrinsic brain tumors within the insula and thalamus carries risk of developing postoperative medical and surgical complications. Neurologic complications may produce visual field, motor, sensory, cognitive, or language deficits.31 They result from violation of functional cortical and subcortical pathways, cerebral edema, hematoma, or vascular injury. In most series, the risk of a new neurologic deficit after craniotomy for resection of a thalamic or insular tumor ranges from 10% to 25%. These risks increase with older age, deep tumor location, tumor proximity to functional regions, and a low Karnofsky Performance Scale score at presentation. Neurologic complications can be minimized by individualizing the surgical approach based on anatomic and functional imaging, cortical mapping techniques, minimizing excessive brain retraction, meticulous hemostasis, and early identification of major vascular structures. Additional complications are related to the surgical wound and surrounding brain parenchyma. These events include surgical wound infections, pneumocephalus, cerebrospinal fluid (CSF) leaks, hydrocephalus, seizure, brain abscess/cerebritis, meningitis, and pseudomeningocele. These complications occur in 1% to 5% of patients undergoing craniotomy for resection of an intrinsic brain tumor, and happen more readily in patients over the age of 65 years and in those undergoing reoperation. Posterior fossa location and reoperations are associated with a higher rate of pseudomeningocele, CSF fistula, and hydrocephalus. Postoperative wound infections occur in 1% to 2% of patients after supratentorial craniotomy, most commonly from Staphylococcus or Staphylococcus species. The risk of postoperative seizures after supratentorial craniotomy is 0.5% to 5%.
Complication Avoidance Neurologic deficits from insular and thalamic tumors are highly variable and depend on tumor location and extent of disease. Preoperative clinical evaluation includes baseline motor and language assessments for dominant-hemisphere tumors. DTIs for white matter tracts and task-based functional brain MRI are helpful adjuvants to decrease perioperative morbidity (Fig. 23.1).32,33 Preoperative imaging provides information regarding tumor location,
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A
B
C
D
E • Fig. 23.1
(A) Axial fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) shows zone 2 insular glioma with the majority of the mass posterior to the foramen of Monro, according to Berger-Sanai classification system. (B) Magnified view reveals proximity of the insular mass to the posterior limb of the internal capsule (outlined in red). (C) Sagittal FLAIR MRI reveals anterior short and posterior long insular gyri, which upon further magnification (D) illustrates the central sulcus of the insula. (E) Cadaveric dissection inverted for surgical views shows the insular apex (*) in addition to operative “windows” between M2 vessels, through which tumor resection occurs (#).
vascularity, mass effect, peritumoral edema, and proximity to areas of potential functional significance. Additionally, MRIs can be reconstructed to create three-dimensional neuronavigation models for use during surgery. Functional MRI uses blood oxygenation level–dependent signal to identify cortical regions of activation with 85% sensitivity for language and 92% sensitivity for motor areas.34,35 Similarly, DTI defines the structure of white matter tracts surrounding a tumor and is commonly used in the planning of both surgical and radiation therapy.36–38
RED FLAGS • • • • •
Large infiltrative tumors Significant mass effect Lesions infiltrating basal ganglia and deep nuclei Previous radiation therapy Patients presenting with neurologic deficits
Avoiding Functional Cortical and Subcortical Pathways The management of intrinsic brain tumors begins with surgery aimed at establishing the pathologic diagnosis and maximal safe resection. Corticosteroids are commonly used preoperatively to reduce symptoms of mass effect and peritumoral vasogenic edema during surgery. Though timing and dose of corticosteroids vary by surgeon preference, a common regimen for adults is 4 to 6 mg of dexamethasone intravenously or by mouth every 6 hours for 48 hours before surgery. Patients presenting with seizures should be initiated on an anticonvulsant, especially if considering intraoperative mapping.31,39,40 Direct cortical stimulation mapping allows for the identification of language, motor, and sensory function during surgery.4 Direct stimulation mapping is the gold standard for identification and preservation of functional areas, which are critical when determining a function-free
CHAPTER 23 Thalamic and Insular Tumors: Minimizing Deficits
corridor. Cortical stimulation depolarizes a focal area of brain, which excites local neurons via diffusion of current using both orthodromic and antidromic propagation. Bipolar or monopolar stimulation may be used. Bipolar stimulation using a 2-mm tip with 5 mm of separation allows for local diffusion and more precise mapping.41 Mapping begins with a stimulation current of 1.5 to 2 mA and increases to a maximum of 6 mA if necessary. A constant current generator delivers 1.25-ms biphasic square waves in 4-s trains at 60 Hz. Electrocorticography is used to detect after-discharge potentials and subclinical seizures, which improves both safety and accuracy. Motor sites are identified as slowing of movement with active mapping or involuntary movement with passive mapping. Cortical language sites are tested at least three times, and a positive site is defined as the inability to count, name objects, or read words during stimulation in at least two of three trials.42 Positive language sites include speech arrest, anomia, and alexia. Speech arrest is defined as discontinuation in number counting without simultaneous motor response.42
Maintaining an Intralesional Resection When approaching insular and thalamic tumors, an intralesional resection is critical given surrounding neurovascular structures. Working through narrow surgical corridors, it may be difficult to remain within the tumor and avoid functional areas. The nonfluorescent amino acid precursor 5-ALA produces an accumulation of fluorescent porphyrins (mainly protoporphyrin IX) in high-grade gliomas.43 Exogenous 5-ALA results in accumulation of intracellular fluorescent protoporphyrins in high-grade glioma, which peaks 4 to 6 hours after administration and remains elevated for 12 hours.44 The active metabolite protoporphyrin IX has an absorption band strongest in the 380 ± 420-nm spectrum, emitting red fluorescence at 635 and 704 nm in the brain. A long-pass filter mounted to the surgical microscope allows for tumor visualization as the operator switches between white and violet light. Thorough removal of all fluorescent tumor improves 6-month and overall survival in malignant glioma without an increase in postoperative neurologic deficits.43 This approach is particularly useful for insular and thalamic gliomas.
Avoiding Vascular Injury The M2 branches of the middle cerebral artery supply the insula and arise from the superior, inferior, and middle trunks of the middle cerebral artery. Short insular perforator arteries may be sacrificed because they supply only the insular cortex; however, the three to five main insular arteries should be maintained throughout resection. After passing over the insular surface, these vessels continue to supply the extreme capsule and claustrum. Additionally, the lenticulostriate artery branches off the main M1 trunk, which supplies the substantia innominate, putamen, globus pallidus, caudate, and internal capsule after penetrating the anterior perforating substance. Preservation of these vessels is critical to prevent stroke (particularly involving the posterior internal capsule).
Conflicts of Interest Shawn L. Hervey-Jumper and Mitchel S. Berger declare that they have no conflicts of interest.
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My Worst Case A 44-year-old male presented with new-onset seizure and was found to have a nonenhancing brain mass concerning for glioma located within zone 1 of the insula on the left. The patient was scheduled for an awake language and motor mapping craniotomy for tumor resection. Tumor was “woody” and firm in consistency. The resection began through three windows into the subinsular space with motor mapping and monitoring during the resection. During follow-up motor mapping, it was determined that the patient was no longer able to move his right arm or leg, with associated facial asymmetry. Papaverine was used intraoperatively, and all insular arteries were inspected. The lenticulostriate artery along the proximal M1 vessel was encased in tumor and never found throughout the case. On postoperative day 2, patient had complete right-sided flaccid paralysis with 3+ deep tendon reflexes. On postoperative day 4, patient began to have a flicker of movement in toes and proximal thigh. Postoperative MRI diffusion-weighted images showed a small area of restricted diffusion within the posterior limb of the internal capsule. Patient returned to clinic 2 months later able to ambulate with 4-/5 right biceps and triceps but continued to have severe functional limitations in the right hand.
References 1. Larjavaara S, Mantyla R, Salminen T, et al. Incidence of gliomas by anatomic location. Neuro Oncol. 2007;9:319–325. 2. 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. 3. Hervey-Jumper SL, Berger MS. Role of surgical resection in low- and high-grade gliomas. Curr Treat Options Neurol. 2014;16:284. 4. Hervey-Jumper SL, Li J, Lau D, et al. Awake craniotomy to maximize glioma resection: methods and technical nuances over a 27-year period. J Neurosurg. 2015;123:325–339. 5. Claus EB, Horlacher A, Hsu L, et al. Survival rates in patients with low-grade glioma after intraoperative magnetic resonance image guidance. Cancer. 2005;103:1227–1233. 6. Ito S, Chandler KL, Prados MD, et al. Proliferative potential and prognostic evaluation of low-grade astrocytomas. J Neurooncol. 1994;19:1–9. 7. Ius T, Isola M, Budai R, et al. Low-grade glioma surgery in eloquent areas: volumetric analysis of extent of resection and its impact on overall survival. A single-institution experience in 190 patients: clinical article. J Neurosurg. 2012;117:1039–1052. 8. Johannesen TB, Langmark F, Lote K. Progress in long-term survival in adult patients with supratentorial low-grade gliomas: a populationbased study of 993 patients in whom tumors were diagnosed between 1970 and 1993. J Neurosurg. 2003;99:854–862. 9. Karim AB, Maat B, Hatlevoll R, et al. A randomized trial on dose-response in radiation therapy of low-grade cerebral glioma: European Organization for Research and Treatment of Cancer (EORTC) Study 22844. Int J Radiat Oncol Biol Phys. 1996;36:549–556. 10. Leighton C, Fisher B, Bauman G, et al. Supratentorial low-grade glioma in adults: an analysis of prognostic factors and timing of radiation. J Clin Oncol. 1997;15:1294–1301. 11. Lote K, Egeland T, Hager B, et al. Survival, prognostic factors, and therapeutic efficacy in low-grade glioma: a retrospective study in 379 patients. J Clin Oncol. 1997;15:3129–3140. 12. Nakamura M, Konishi N, Tsunoda S, et al. Analysis of prognostic and survival factors related to treatment of low-grade astrocytomas in adults. Oncology. 2000;58:108–116. 13. Nicolato A, Gerosa MA, Fina P, Iuzzolino P, Giorgiutti F, Bricolo A. Prognostic factors in low-grade supratentorial astrocytomas: a
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uni-multivariate statistical analysis in 76 surgically treated adult patients. Surg Neurol. 1995;44:208–221, discussion 221–223. 14. North CA, North RB, Epstein JA, Piantadosi S, Wharam MD. Low-grade cerebral astrocytomas. Survival and quality of life after radiation therapy. Cancer. 1990;66:6–14. 15. Peraud A, Ansari H, Bise K, Reulen HJ. Clinical outcome of supratentorial astrocytoma WHO grade II. Acta Neurochir (Wien). 1998;140:1213–1222. 16. Philippon JH, Clemenceau SH, Fauchon FH, Foncin JF. Supratentorial low-grade astrocytomas in adults. Neurosurgery. 1993;32: 554–559. 17. Rajan B, Pickuth D, Ashley S, et al. The management of histologically unverified presumed cerebral gliomas with radiotherapy. Int J Radiat Oncol Biol Phys. 1994;28:405–413. 18. Sanai N, Berger MS. Glioma extent of resection and its impact on patient outcome. Neurosurgery. 2008;62:753–764, discussion 264–266. 19. Scerrati M, Roselli R, Iacoangeli M, Pompucci A, Rossi GF. Prognostic factors in low grade (WHO grade II) gliomas of the cerebral hemispheres: the role of surgery. J Neurol Neurosurg Psychiatry. 1996;61:291–296. 20. Shaw E, Arusell R, Scheithauer B, et al. Prospective randomized trial of low- versus high-dose radiation therapy in adults with supratentorial low-grade glioma: initial report of a North Central Cancer Treatment Group/Radiation Therapy Oncology Group/Eastern Cooperative Oncology Group study. J Clin Oncol. 2002;20:2267–2276. 21. Shibamoto Y, Kitakabu Y, Takahashi M, et al. Supratentorial lowgrade astrocytoma. Correlation of computed tomography findings with effect of radiation therapy and prognostic variables. Cancer. 1993;72:190–195. 22. Snyder LA, Wolf AB, Oppenlander ME, et al. The impact of extent of resection on malignant transformation of pure oligodendrogliomas. J Neurosurg. 2014;120:309–314. 23. van Veelen ML, Avezaat CJ, Kros JM, van Putten W, Vecht C. Supratentorial low grade astrocytoma: prognostic factors, dedifferentiation, and the issue of early versus late surgery. J Neurol Neurosurg Psychiatry. 1998;64:581–587. 24. Vecht CJ, Avezaat CJ, van Putten WL, Eijkenboom WM, Stefanko SZ. The influence of the extent of surgery on the neurological function and survival in malignant glioma. A retrospective analysis in 243 patients. J Neurol Neurosurg Psychiatry. 1990;53:466–471. 25. Whitton AC, Bloom HJ. Low grade glioma of the cerebral hemispheres in adults: a retrospective analysis of 88 cases. Int J Radiat Oncol Biol Phys. 1990;18:783–786. 26. Yeh SA, Ho JT, Lui CC, Huang YJ, Hsiung CY, Huang EY. Treatment outcomes and prognostic factors in patients with supratentorial low-grade gliomas. Br J Radiol. 2005;78:230–235. 27. Tanriover N, Rhoton AL Jr, Kawashima M, Ulm AJ, Yasuda A. Microsurgical anatomy of the insula and the sylvian fissure. J Neurosurg. 2004;100:891–922. 28. Benet A, Hervey-Jumper SL, Sanchez JJ, Lawton MT, Berger MS. Surgical assessment of the insula. Part 1: surgical anatomy and
morphometric analysis of the transsylvian and transcortical approaches to the insula. J Neurosurg. 2016;124:469–481. 29. Sanai N, Polley MY, Berger MS. Insular glioma resection: assessment of patient morbidity, survival, and tumor progression. J Neurosurg. 2010;112:1–9. 30. Sai Kiran NA, Thakar S, Dadlani R, et al. Surgical management of thalamic gliomas: case selection, technical considerations, and review of literature. Neurosurg Rev. 2013;36:383–393. 31. Chang SM, Parney IF, Huang W, et al. Patterns of care for adults with newly diagnosed malignant glioma. JAMA. 2005;293:557–564. 32. Deng X, Zhang Y, Xu L, et al. Comparison of language cortex reorganization patterns between cerebral arteriovenous malformations and gliomas: a functional MRI study. J Neurosurg. 2015;122:996–1003. 33. Ille S, Sollmann N, Hauck T, et al. Combined noninvasive language mapping by navigated transcranial magnetic stimulation and functional MRI and its comparison with direct cortical stimulation. J Neurosurg. 2015;123:212–225. 34. Bogomolny DL, Petrovich NM, Hou BL, Peck KK, Kim MJ, Holodny AI. Functional MRI in the brain tumor patient. Top Magn Reson Imaging. 2004;15:325–335. 35. Nimsky C, Ganslandt O, Von Keller B, Romstock J, Fahlbusch R. Intraoperative high-field-strength MR imaging: implementation and experience in 200 patients. Radiology. 2004;233:67–78. 36. Alexander AL, Lee JE, Lazar M, Field AS. Diffusion tensor imaging of the brain. Neurother. 2007;4:316–329. 37. Bello L, Gambini A, Castellano A, et al. Motor and language DTI Fiber Tracking combined with intraoperative subcortical mapping for surgical removal of gliomas. Neuroimage. 2008;39:369–382. 38. Berman JI, Berger MS, Chung SW, Nagarajan SS, Henry RG. Accuracy of diffusion tensor magnetic resonance imaging tractography assessed using intraoperative subcortical stimulation mapping and magnetic source imaging. J Neurosurg. 2007;107:488–494. 39. Chang EF, Potts MB, Keles GE, et al. Seizure characteristics and control following resection in 332 patients with low-grade gliomas. J Neurosurg. 2008;108:227–235. 40. Lima GL, Duffau H. Is there a risk of seizures in “preventive” awake surgery for incidental diffuse low-grade gliomas? J Neurosurg. 2015;122:1397–1405. 41. 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;86:183–192. 42. Sanai N, Mirzadeh Z, Berger MS. Functional outcome after language mapping for glioma resection. N Engl J Med. 2008;358:18–27. 43. Stummer W, Pichlmeier U, Meinel T, et al. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol. 2006;7:392–401. 44. Stummer W, Reulen HJ, Novotny A, Stepp H, Tonn JC. Fluorescenceguided resections of malignant gliomas–an overview. Acta Neurochir Suppl. 2003;88:9–12.
Thalamic and Insular Tumors: Minimizing Deficits SHAWN L. HERVEY-JUMPER, MITCHEL S. BERGER
HIGHLIGHTS • Insular and thalamic intrinsic brain tumors pose perioperative risk due to their proximity to functional cortical and subcortical pathways and neurovascular structures. • Preservation of M2 insular and lenticulostriate arteries is critical to prevent postoperative stroke. • Cortical and subcortical mapping to identify language and motor sites, particularly the posterior limb of the internal capsule, limits the risk of postoperative deficits.
Introduction The role of surgery in the treatment of intrinsic brain tumors is to establish the correct histologic and molecular diagnosis, relieve mass effect, and provide maximal safe resection to improve both overall and progression-free survival. Nearly 50% of tumors are within difficult-to-access areas, with either presumed functional significance or close association with vascular structures. Surgical decisions therefore must balance reduction of tumor volume with avoidance of important neurovascular structures. Gliomas are the most common primary intrinsic brain tumor. The majority of gliomas are located in the cerebral hemispheres; however, 6.4% are located within the deep structures of the cerebrum, including primarily the insula and thalamus.1,2 Tumors within the insula and thalamus remain a challenge to manage given proximity to functionally significant areas and intimate relationship with vascular structures. Surgical techniques such as awake craniotomy with cortical and subcortical mapping permit maximal extent of resection while minimizing postoperative morbidity.3,4 Intraoperative violation of cortical and subcortical functional pathways may lead to immediate neurologic sequelae, negatively impacting quality of life and survival. Additionally, injuries to branches of the middle cerebral artery or lenticulostriate arteries are well reported and often have catastrophic consequences, which can range from (1) stroke to (2) hemorrhage, (3) vasospasm, or (4) thrombosis. This chapter will discuss surgical approaches for intrinsic brain tumors located within the thalamus and insula.
Indications for Surgery Gliomas and brain metastasis are the most common deep-seated intrinsic brain tumors, with the most robust body of literature in support of maximal safe resection. There are four histologic grades 120
for gliomas recognized by the World Health Organization (WHO). Grade I tumors have minimal proliferative potential and circumscribed growth. WHO grade II gliomas include diffuse astrocytoma, pleomorphic xanthoastrocytoma, and oligodendroglioma. These tumors have low mitotic activity; however, given their infiltrative nature, they have a tendency to recur, albeit most commonly near the site of initial presentation. WHO grade III gliomas, such as anaplastic astrocytoma, display nuclear anaplasia and increased cellularity. Glioblastomas are WHO grade IV gliomas and represent the most common primary brain tumor in adults. Numerous studies have examined the relationship between extent of resection and volume of residual tumor, overall survival, progression-free survival, and time to malignant transformation among patients with low- and high-grade gliomas.2,5–26 Although no class I data exist, the majority of published reports suggest that greater extent of resection improves overall survival and progression-free survival, and lengthens the time to malignant transformation.
Anatomic Insights and Surgical Approach Intrinsic brain tumors within the insula or thalamus were previously considered inoperable due to the high risk of perioperative complications. However, a combination of improved microsurgical techniques, neuroanesthesia, and advanced structural and functional imaging permit greater access to many insular and thalamic tumors. Surgical approach and technical considerations for tumors within the insula and thalamus are discussed in this chapter.
Approaches to the Insula Opercular landmarks at the cerebral surface may be beneficial to localize structures within the insula. The insula is a triangular-shaped structure within the sylvian fissure, which lies deep to the frontal, parietal, and temporal lobes. The optimal approach to insular lesions may require either splitting the sylvian fissure or resecting the overlying operculum; therefore it’s critical to know both sylvian fissure anatomy and cortical opercular landmarks. The sylvian fissure consists of a central stem in addition to horizontal, anterior ascending, and posterior rami. The longest portion of the sylvian fissure is the posterior ramus, which extends posterior and superior and terminates in the inferior parietal lobule. The anterior horizontal and anterior ascending rami are shorter and divide the inferior frontal gyrus into the pars opercularis, orbitalis, and triangularis. The insular surface faces laterally and is enclosed by the anterior
CHAPTER 23 Thalamic and Insular Tumors: Minimizing Deficits
and posterior limiting (also known as circular) sulci. The limiting sulcus has anterior, superior, and inferior parts.27 The insular cortex is composed of an anterior limen insula, central sulcus, three anterior short gyri, and two posteriorly placed long gyri. The central sulcus of the insula is a continuation of the central sulcus of the cerebral hemispheres. Two anterior sulci separate the three short gyri, and a single sulcus separates the two long posterior gyri. The insular pole is located at the anteroinferior edge of the insula, where the short gyri converge to form a rounded area lateral to the limen. The insular apex is the highest and most prominent laterally projecting area on the insular convexity. Lying underneath the cortical surface of the pars opercularis is the superior portion of the anterior and middle short insular gyri. Posteriorly, the supramarginal gyrus overlies the superior limiting sulcus and the superior portion of the posterior long gyri. The limen insula overlies the uncinate fasciculus.27,28 Additionally, the anterior perforated substance lies medial to the limen. The middle cerebral artery bifurcates at the limen insula, forming M2 branches, which overlay the insular surface. Insular tumors are among the most challenging neurosurgical lesions to manage. Tumor location and hemisphere of language dominance determine whether a transcortical or transsylvian approach should be considered.28 Patients are put in a semilateral position with the head parallel to the floor.29 For tumors located predominantly above or below the sylvian fissure, the vertex of the head is positioned 15 degrees toward the floor. The craniotomy is tailored based on tumor location and involvement of the overlying frontal or temporal operculum. Insular tumors may be approached based on their location within four zones. The sylvian line divides the insular cortex into dorsal and ventral parts. The foramen of Monro divides the insula into rostral and caudal portions, creating four zones.4 The transcortical exposure offers the maximal insular exposure with the widest surgical window and surgical freedom.28 The insular surface is exposed and surgical resection continues as the vessels of the sylvian fissure are skeletonized, which creates “surgical windows.” The resection is continued by working under the sylvian fissure along the uncinate fasciculus. Cortical and subcortical sensorimotor and language mapping may be utilized, particularly for posterior zone 2 and 3 tumors. The suprasylvian lenticulostriate arteries must be identified and preserved, and subcortical motor mapping of the corticospinal tract marks the medial border of the resection.
Approaches to the Thalamus The choice of surgical approach for thalamic tumor resection balances tumor location, vascularity, and the location of the posterior limb of the internal capsule. Thalamic tumors are relatively rare, representing 2% of all brain tumors.30 Although lesions in this location have historically been surgically treated with stereotactic biopsy alone, advanced structural imaging and microsurgical techniques have allowed for surgical resection with acceptable perioperative morbidity. The surgical corridor of choice uses the shortest route to the tumor avoiding the internal capsule and normal thalamus. These decisions are made based on careful study of preoperative axial and coronal magnetic resonance imaging (MRI) with addition of diffusion tensor imaging (DTI) tractography. Operative approaches include (1) middle temporal gyrus approach, (2) occipital transtentorial approach, (3) middle frontal gyrus approach, (4) transcallosal approach, and (5) combined approaches.30 Surgical resection is reserved for contrast-enhancing tumors with clear margins on preoperative imaging. Nonenhancing tumors
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with poorly defined margins should be treated with biopsy alone given their propensity to have functional tissue within the lesion. Surgical approach is based on tumor location (anterior or posterior within the thalamus) and proximity to the posterior limb of the internal capsule. The middle temporal gyrus approach is used predominantly for posterolateral tumors close to the temporal horn of the lateral ventricle. The occipital transtentorial approach offers maximal exposure for posterior medially placed thalamic tumors in close proximity to the third ventricle. The middle frontal gyrus approach is used for anterolateral thalamic tumors extending superiorly into the frontal lobe. The transcallosal approach is rarely used but is saved for anteromedial thalamic tumors. The majority of deep-seated intrinsic tumors cause anterolateral displacement of the posterior limb of the internal capsule, making the middle temporal gyrus corridor the common approach. After a temporal corticectomy, the tumor is approached through the lateral ventricle along the posterolateral margin of the tumor. Upon reaching the temporal horn of the lateral ventricle, the tumor is approached through the choroidal fissure. This approach ensures an entry corridor inferior to the insula and posterior to the internal capsule.
Complications Surgery for intrinsic brain tumors within the insula and thalamus carries risk of developing postoperative medical and surgical complications. Neurologic complications may produce visual field, motor, sensory, cognitive, or language deficits.31 They result from violation of functional cortical and subcortical pathways, cerebral edema, hematoma, or vascular injury. In most series, the risk of a new neurologic deficit after craniotomy for resection of a thalamic or insular tumor ranges from 10% to 25%. These risks increase with older age, deep tumor location, tumor proximity to functional regions, and a low Karnofsky Performance Scale score at presentation. Neurologic complications can be minimized by individualizing the surgical approach based on anatomic and functional imaging, cortical mapping techniques, minimizing excessive brain retraction, meticulous hemostasis, and early identification of major vascular structures. Additional complications are related to the surgical wound and surrounding brain parenchyma. These events include surgical wound infections, pneumocephalus, cerebrospinal fluid (CSF) leaks, hydrocephalus, seizure, brain abscess/cerebritis, meningitis, and pseudomeningocele. These complications occur in 1% to 5% of patients undergoing craniotomy for resection of an intrinsic brain tumor, and happen more readily in patients over the age of 65 years and in those undergoing reoperation. Posterior fossa location and reoperations are associated with a higher rate of pseudomeningocele, CSF fistula, and hydrocephalus. Postoperative wound infections occur in 1% to 2% of patients after supratentorial craniotomy, most commonly from Staphylococcus or Staphylococcus species. The risk of postoperative seizures after supratentorial craniotomy is 0.5% to 5%.
Complication Avoidance Neurologic deficits from insular and thalamic tumors are highly variable and depend on tumor location and extent of disease. Preoperative clinical evaluation includes baseline motor and language assessments for dominant-hemisphere tumors. DTIs for white matter tracts and task-based functional brain MRI are helpful adjuvants to decrease perioperative morbidity (Fig. 23.1).32,33 Preoperative imaging provides information regarding tumor location,
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A
B
C
D
E • Fig. 23.1
(A) Axial fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) shows zone 2 insular glioma with the majority of the mass posterior to the foramen of Monro, according to Berger-Sanai classification system. (B) Magnified view reveals proximity of the insular mass to the posterior limb of the internal capsule (outlined in red). (C) Sagittal FLAIR MRI reveals anterior short and posterior long insular gyri, which upon further magnification (D) illustrates the central sulcus of the insula. (E) Cadaveric dissection inverted for surgical views shows the insular apex (*) in addition to operative “windows” between M2 vessels, through which tumor resection occurs (#).
vascularity, mass effect, peritumoral edema, and proximity to areas of potential functional significance. Additionally, MRIs can be reconstructed to create three-dimensional neuronavigation models for use during surgery. Functional MRI uses blood oxygenation level–dependent signal to identify cortical regions of activation with 85% sensitivity for language and 92% sensitivity for motor areas.34,35 Similarly, DTI defines the structure of white matter tracts surrounding a tumor and is commonly used in the planning of both surgical and radiation therapy.36–38
RED FLAGS • • • • •
Large infiltrative tumors Significant mass effect Lesions infiltrating basal ganglia and deep nuclei Previous radiation therapy Patients presenting with neurologic deficits
Avoiding Functional Cortical and Subcortical Pathways The management of intrinsic brain tumors begins with surgery aimed at establishing the pathologic diagnosis and maximal safe resection. Corticosteroids are commonly used preoperatively to reduce symptoms of mass effect and peritumoral vasogenic edema during surgery. Though timing and dose of corticosteroids vary by surgeon preference, a common regimen for adults is 4 to 6 mg of dexamethasone intravenously or by mouth every 6 hours for 48 hours before surgery. Patients presenting with seizures should be initiated on an anticonvulsant, especially if considering intraoperative mapping.31,39,40 Direct cortical stimulation mapping allows for the identification of language, motor, and sensory function during surgery.4 Direct stimulation mapping is the gold standard for identification and preservation of functional areas, which are critical when determining a function-free
CHAPTER 23 Thalamic and Insular Tumors: Minimizing Deficits
corridor. Cortical stimulation depolarizes a focal area of brain, which excites local neurons via diffusion of current using both orthodromic and antidromic propagation. Bipolar or monopolar stimulation may be used. Bipolar stimulation using a 2-mm tip with 5 mm of separation allows for local diffusion and more precise mapping.41 Mapping begins with a stimulation current of 1.5 to 2 mA and increases to a maximum of 6 mA if necessary. A constant current generator delivers 1.25-ms biphasic square waves in 4-s trains at 60 Hz. Electrocorticography is used to detect after-discharge potentials and subclinical seizures, which improves both safety and accuracy. Motor sites are identified as slowing of movement with active mapping or involuntary movement with passive mapping. Cortical language sites are tested at least three times, and a positive site is defined as the inability to count, name objects, or read words during stimulation in at least two of three trials.42 Positive language sites include speech arrest, anomia, and alexia. Speech arrest is defined as discontinuation in number counting without simultaneous motor response.42
Maintaining an Intralesional Resection When approaching insular and thalamic tumors, an intralesional resection is critical given surrounding neurovascular structures. Working through narrow surgical corridors, it may be difficult to remain within the tumor and avoid functional areas. The nonfluorescent amino acid precursor 5-ALA produces an accumulation of fluorescent porphyrins (mainly protoporphyrin IX) in high-grade gliomas.43 Exogenous 5-ALA results in accumulation of intracellular fluorescent protoporphyrins in high-grade glioma, which peaks 4 to 6 hours after administration and remains elevated for 12 hours.44 The active metabolite protoporphyrin IX has an absorption band strongest in the 380 ± 420-nm spectrum, emitting red fluorescence at 635 and 704 nm in the brain. A long-pass filter mounted to the surgical microscope allows for tumor visualization as the operator switches between white and violet light. Thorough removal of all fluorescent tumor improves 6-month and overall survival in malignant glioma without an increase in postoperative neurologic deficits.43 This approach is particularly useful for insular and thalamic gliomas.
Avoiding Vascular Injury The M2 branches of the middle cerebral artery supply the insula and arise from the superior, inferior, and middle trunks of the middle cerebral artery. Short insular perforator arteries may be sacrificed because they supply only the insular cortex; however, the three to five main insular arteries should be maintained throughout resection. After passing over the insular surface, these vessels continue to supply the extreme capsule and claustrum. Additionally, the lenticulostriate artery branches off the main M1 trunk, which supplies the substantia innominate, putamen, globus pallidus, caudate, and internal capsule after penetrating the anterior perforating substance. Preservation of these vessels is critical to prevent stroke (particularly involving the posterior internal capsule).
Conflicts of Interest Shawn L. Hervey-Jumper and Mitchel S. Berger declare that they have no conflicts of interest.
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My Worst Case A 44-year-old male presented with new-onset seizure and was found to have a nonenhancing brain mass concerning for glioma located within zone 1 of the insula on the left. The patient was scheduled for an awake language and motor mapping craniotomy for tumor resection. Tumor was “woody” and firm in consistency. The resection began through three windows into the subinsular space with motor mapping and monitoring during the resection. During follow-up motor mapping, it was determined that the patient was no longer able to move his right arm or leg, with associated facial asymmetry. Papaverine was used intraoperatively, and all insular arteries were inspected. The lenticulostriate artery along the proximal M1 vessel was encased in tumor and never found throughout the case. On postoperative day 2, patient had complete right-sided flaccid paralysis with 3+ deep tendon reflexes. On postoperative day 4, patient began to have a flicker of movement in toes and proximal thigh. Postoperative MRI diffusion-weighted images showed a small area of restricted diffusion within the posterior limb of the internal capsule. Patient returned to clinic 2 months later able to ambulate with 4-/5 right biceps and triceps but continued to have severe functional limitations in the right hand.
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