Acta Neurochirurgica

, Volume 154, Issue 4, pp 569–574 | Cite as

The challenge to remove diffuse low-grade gliomas while preserving brain functions

  • Hugues DuffauEmail author
Review Article


WHO grade II glioma, i.e. diffuse low-grade glioma, is a pre-malignant tumour, usually revealed by seizures in young patients with a normal life. This tumour has a constant growth, and will inescapably become anaplastic. Surgical resection significantly increases the overall survival by delaying the malignant transformation. Thus, the dilemma is to perform early surgery in order to optimise the extent of resection (and thus the median survival) by removing smaller tumours while preserving the quality of life. To this end, the new concept proposed in this review is to achieve surgical resection according to functional and not to oncological boundaries. In other words, the principle is to first understand the cerebral anatomo-functional organisation at the individual level (because of a major inter-individual variability), with the aim of resecting a part of the brain invaded by a diffuse chronic disease, on the condition nonetheless that this part of the brain can be functionally compensated—i.e. with no consequences on the quality of life. To this end, in addition to the preoperative functional neuroimaging and the intraoperative electrical cortical mapping in awake patients, it is also crucial to map both horizontal cortico-cortical connectivity (long-distance association fibres) as well as vertical cortico-subcortical connectivity (projection fibres), with the aim to preserve the networks underlying the minimal common core of the brain. Interestingly, this “hodotopical” workframe, based on the study of both cortical epicentres and subcortical pathways, opens the door to mechanisms of functional reshaping. These recent technical and conceptual advances in the hodotopical and plastic view of brain processing have allowed a dramatic improvement of the benefit-to-risk ratio of surgery, concerning both oncological and functional outcomes. In summary, it is time to move towards “functional neurooncology” and “preventive neurosurgery” in low-grade gliomas. Stronger interactions with fundamental neurosciences should be developed, in order (1) to build updated models of cognition and brain plasticity; (2) to elaborate biomathematical models of low-grade glioma growth and migration; (3) to study in silico the dynamic interactions between the natural course of this disease and the adaptative behaviour of its host (the brain), with the goal to adapt the best individualised therapeutic strategy.


Low-grade glioma Awake surgery Intraoperative electrical mapping Brain plasticity Anatomo-functional connectivity 


Conflicts of interest



  1. 1.
    Benzagmout M, Gatignol P, Duffau H (2007) Resection of World Health Organization grade II gliomas involving Broca’s area: methodological and functional considerations. Neurosurgery 61:741–752PubMedCrossRefGoogle Scholar
  2. 2.
    Blonski M, Taillandier L, Herbet G, Maldonado I, Beauchesne P, Fabbro M, Campello C, Gozé C, Rigau V, Moritz-Gasser S, Kerr C, Rudà R, Soffietti R, Bauchet L, Duffau H (2012) Combination of neoadjuvant chemotherapy followed by surgical resection as a new strategy for WHO grade II gliomas: a study of cognitive status and quality of life. J Neurooncol 106:353–366PubMedCrossRefGoogle Scholar
  3. 3.
    Chang EF, Potts MB, Keles GE, Lamborn KR, Chang SM, Barbaro NM, Berger MS (2008) Seizure characteristics and control following resection in 332 patients with low-grade gliomas. J Neurosurg 108:227–235PubMedCrossRefGoogle Scholar
  4. 4.
    Chang E, Clark A, Smith J, Polley MY, Chang SM, Barbaro NM, Parsa AT, McDermott MW, Berger MS (2011) Functional mapping–guided resection of low-grade gliomas in eloquent areas of the brain: improvement of long-term survival. J Neurosurg 114:566–573PubMedCrossRefGoogle Scholar
  5. 5.
    Chang EF, Wang DD, Perry DW, Barbaro NM, Berger MS (2011) Homotopic organization of essential language sites in right and bilateral cerebral hemispheric dominance. J Neurosurg 114:893–902PubMedCrossRefGoogle Scholar
  6. 6.
    de Benedictis A, Duffau H (2011) Brain hodotopy: from the esoteric concept to the practical surgical applications. Neurosurgery 68:1709–1723PubMedCrossRefGoogle Scholar
  7. 7.
    de Benedictis A, Moritz-Gasser S, Duffau H (2010) Awake mapping optimizes the extent of resection for low-grade gliomas in eloquent areas. Neurosurgery 66:1074–1084PubMedCrossRefGoogle Scholar
  8. 8.
    Desmurget M, Bonnetblanc F, Duffau H (2007) Contrasting acute and slow growing lesions: a new door to brain plasticity. Brain 130:898–914PubMedCrossRefGoogle Scholar
  9. 9.
    De Witt HP, Moritz-Gasser S, Gatignol P, Duffau H (2011) Is the human left middle longitudinal fascicle essential for language? A brain electrostimulation study. Hum Brain Mapp 32:962–973CrossRefGoogle Scholar
  10. 10.
    Duffau H (2001) Acute functional reorganisation of the human motor cortex during resection of central lesions: a study using intraoperative brain mapping. J Neurol Neurosurg Psychiatry 70:506–513PubMedCrossRefGoogle Scholar
  11. 11.
    Duffau H (2005) Lessons from brain mapping in surgery for low-grade glioma: insights into associations between tumour and brain plasticity. Lancet Neurol 4:476–486PubMedCrossRefGoogle Scholar
  12. 12.
    Duffau H (2006) Brain plasticity: from pathophysiological mechanisms to therapeutic applications. J Clin Neurosci 13:885–897PubMedCrossRefGoogle Scholar
  13. 13.
    Duffau H (2008) The anatomo-functional connectivity of language revisited: new insights provided by electrostimulation and tractography. Neuropsychologia 4:927–934CrossRefGoogle Scholar
  14. 14.
    Duffau H (2008) Brain plasticity and tumors. Adv Tech Stand Neurosurg 33:3–33PubMedCrossRefGoogle Scholar
  15. 15.
    Duffau H (2009) Does post-lesional subcortical plasticity exist in the human brain? Neurosci Res 65:131–135PubMedCrossRefGoogle Scholar
  16. 16.
    Duffau H (2009) A personal consecutive series of surgically treated 51 cases of insular WHO grade II glioma: advances and limitations. J Neurosurg 110:696–708PubMedCrossRefGoogle Scholar
  17. 17.
    Duffau H (2009) Surgery of low-grade gliomas: towards a ‘functional neurooncology’. Curr Opin Oncol 21:543–549PubMedCrossRefGoogle Scholar
  18. 18.
    Duffau H (2010) Surgery in eloquent areas: from brain hodotopy and plasticity to functional neurooncology. Neurosurg Focus 28(2): IntroGoogle Scholar
  19. 19.
    Duffau H (2010) Awake surgery for non-language mapping. Neurosurgery 66:523–528PubMedCrossRefGoogle Scholar
  20. 20.
    Duffau H (2011) Toward the application of the hodotopical concept to epilepsy surgery. World Neurosurg 75:431–433PubMedCrossRefGoogle Scholar
  21. 21.
    Duffau H (ed) (2011) Brain mapping: from neural basis of cognition to surgical applications. Springer, Wien New YorkGoogle Scholar
  22. 22.
    Duffau H, Capelle L (2004) Preferential brain locations of low grade gliomas. Cancer 100:2622–2626PubMedCrossRefGoogle Scholar
  23. 23.
    Duffau H, Capelle L, Sichez N, Denvil D, Lopes M, Sichez JP, Bitar A, Fohanno D (2002) Intraoperative mapping of the subcortical language pathways using direct stimulations. An anatomo-functional study Brain 125:199–214Google Scholar
  24. 24.
    Duffau H, Gatignol P, Mandonnet E, Capelle L, Taillandier L (2008) Intraoperative subcortical stimulation mapping of language pathways in a consecutive series of 115 patients with Grade II glioma in the left dominant hemisphere. J Neurosurg 109:461–471PubMedCrossRefGoogle Scholar
  25. 25.
    Duffau H, Gatignol P, Mandonnet E, Peruzzi P, Tzourio-Mazoyer N, Capelle L (2005) New insights into the anatomo-functional connectivity of the semantic system: a study using cortico-subcortical stimulations. Brain 128:797–810PubMedCrossRefGoogle Scholar
  26. 26.
    Duffau H, Khalil I, Gatignol P, Denvil D, Capelle L (2004) Surgical removal of corpus callosum infiltrated by low-grade glioma: functional outcome and oncological considerations. J Neurosurg 100:431–437PubMedCrossRefGoogle Scholar
  27. 27.
    Duffau H, Leroy M, Gatignol P (2008) Cortico-subcortical organization of language networks in the right hemisphere: an electrostimulation study in left-handers. Neuropsychologia 46:3197–209PubMedCrossRefGoogle Scholar
  28. 28.
    Duffau H, Lopes M, Arthuis F, Bitar A, Sichez JP, van Effenterre R, Capelle L (2005) Contribution of intraoperative electrical stimulations in surgery of low grade gliomas: a comparative study between two series without (1985–96) and with (1996–2003) functional mapping in the same institution. J Neurol Neurosurg Psychiatry 76:845–851PubMedCrossRefGoogle Scholar
  29. 29.
    Duffau H, Pallud J, Mandonnet E (2011) Evidence for the genesis of WHO grade II glioma in an asymptomatic young adult using repeated MRIs. Acta Neurochir (Wien) 153:473–477CrossRefGoogle Scholar
  30. 30.
    Duffau H, Taillandier L, Capelle L (2006) Radical surgery after chemotherapy: a new therapeutic strategy to envision in grade II glioma. J Neurooncol 80:171–176PubMedCrossRefGoogle Scholar
  31. 31.
    Robles S, Duffau H (2010) Surgical management of World Health Organization grade II gliomas in eloquent areas: the necessity of preserving a margina round functional structures. Neurosurg Focus 28:E8CrossRefGoogle Scholar
  32. 32.
    Gil Robles S, Gatignol P, Capelle L, Mitchell MC, Duffau H (2005) The role of dominant striatum in language: a study using intraoperative electrical stimulations. J Neurol Neurosurg Psychiatry 76:940–946PubMedCrossRefGoogle Scholar
  33. 33.
    Gil Robles S, Gatignol P, Lehéricy S, Duffau H (2008) Long-term brain plasticity allowing multiple-stages surgical approach for WHO grade II gliomas in eloquent areas: a combined study using longitudinal functional MRI and intraoperative electrical stimulation. J Neurosurg 109:615–624CrossRefGoogle Scholar
  34. 34.
    Ius T, Angelini E, Thiebaut de Schotten M, Mandonnet E, Duffau H (2011) Evidence for potentials and limitations of brain plasticity using an atlas of functional resectability of WHO grade II gliomas: towards a “minimal common brain”. Neuroimage 56:992–1000PubMedCrossRefGoogle Scholar
  35. 35.
    Klein M, de Witt Hamer P (2011) Neurocognitive outcome and resective brain tumor surgery in adults. In: Duffau H (ed) Brain mapping: from neural basis of cognition to surgical applications. Springer, Wien New YorkGoogle Scholar
  36. 36.
    Krainik A, Duffau H, Capelle L, Cornu P, Boch AL, Mangin JF, Le Bihan D, Marsault C, Chiras J, Lehéricy S (2004) Role of the healthy hemisphere in recovery after resection of the supplementary motor area. Neurology 62:1323–1332PubMedGoogle Scholar
  37. 37.
    Leclercq D, Duffau H, Delmaire C, Capelle L, Gatignol P, Ducros M, Chiras J, Lahéricy S (2010) Comparison of diffusion tensor imaging tractography of language tracts and intraoperative subcortical stimulations. J Neurosurg 112:503–511PubMedCrossRefGoogle Scholar
  38. 38.
    Maldonado IL, Moritz-Gasser S, Duffau H (2011) Does the left superior longitudinal fascicle subserve language semantics? A brain electrostimulation study. Brain Struct Funct 216:263–274PubMedCrossRefGoogle Scholar
  39. 39.
    Mandonnet E, Capelle L, Duffau H (2006) Extension of paralimbic low grade gliomas: toward an anatomical classification based on white matter invasion patterns. J Neurooncol 78:179–185PubMedCrossRefGoogle Scholar
  40. 40.
    Mandonnet E, Delattre JY, Tanguy ML, Swanson KR, Carpentier AF, Duffau H, Cornu P, Van Effenterre R, Alvord EC Jr, Capelle L (2003) Continuous growth of mean tumoral diameter in a subset of grade II gliomas. Ann Neurol 53:524–528PubMedCrossRefGoogle Scholar
  41. 41.
    Mandonnet E, Nouet A, Gatignol P, Capelle L, Duffau H (2007) Does the left inferior longitudinal fasciculus play a role in language? A brain stimulation study. Brain 130:623–629PubMedCrossRefGoogle Scholar
  42. 42.
    Mandonnet E, Pallud J, Clatz O, Taillandier L, Konukoglu E, Duffau H, Capelle L (2008) Computational modeling of the WHO grade II glioma dynamics: principles and applications to management paradigm. Neurosurg Rev 31:263–269PubMedCrossRefGoogle Scholar
  43. 43.
    Pallud J, Fontaine D, Duffau H, Mandonnet E, Sanai N, Taillandier L, Peruzzi P, Guillevin R, Bauchet L, Bernier V, Baron MH, Guyotat J, Capelle L (2010) Natural history of incidental World Health Organization grade II gliomas. Ann Neurol 68:727–733PubMedCrossRefGoogle Scholar
  44. 44.
    Pallud J, Mandonnet E, Duffau H, Kujas M, Guillevin R, Galanaud D, Taillandier L, Capelle L (2006) Prognostic value of initial magnetic resonance imaging growth rates for World Health Organization grade II gliomas. Ann Neurol 60:380–383PubMedCrossRefGoogle Scholar
  45. 45.
    Sacko O, Lauwers-Cances V, Brauge D, Sesay M, Brenner A, Roux FE (2011) Awake craniotomy versus surgery under general anesthesia for resection of supratentorial lesions. Neurosurgery 68:1192–1198PubMedGoogle Scholar
  46. 46.
    Sanai N, Mirzadeh Z, Berger MS (2008) Functional outcome after language mapping for glioma resection. N Engl J Med 358:18–27PubMedCrossRefGoogle Scholar
  47. 47.
    Sarubbo S, Le Bars E, Moritz-Gasser S, Duffau H (in press) Complete recovery after surgical resection of left Wernicke’s area in awake patient: a brain stimulation and functional MRI study. Neurosurg RevGoogle Scholar
  48. 48.
    Smith JS, Chang EF, Lamborn KR, Chang SM, Prados MD, Cha S, Tihan T, Vandenberg S, McDermott MW, Berger MS (2008) Role of extent of resection in the long-term outcome of low-grade hemispheric gliomas. J Clin Oncol 26:1338–1345PubMedCrossRefGoogle Scholar
  49. 49.
    Smith A, Duffau H (2011) Seizures and the natural history of WHO grade II gliomas: a review. Neurosurgery 68:1326–1333Google Scholar
  50. 50.
    Soffietti R, Baumert BG, Bello L, von Deimling A, Duffau H, Frénay M, Grisold W, Grant R, Graus F, Hoang-Xuan K, Klein M, Melin B, Rees J, Siegal T, Smits A, Stupp R, Wick W (2010) Guidelines on management of low-grade gliomas: report of an EFNS–EANO* Task Force. Eur J Neurol 17:1124–1133PubMedCrossRefGoogle Scholar
  51. 51.
    Teixidor P, Gatignol P, Leroy M, Masuet-Aumatell C, Capelle L, Duffau H (2007) Assessment of verbal working memory before and after surgery for low-grade glioma. J Neurooncol 81:305–313PubMedCrossRefGoogle Scholar
  52. 52.
    Thiebaut de Schotten M, Urbanski M, Duffau H, Volle E, Lévy R, Dubois B, Bartolomeo P (2005) Direct evidence for a parietal-frontal pathway subserving spatial awareness in humans. Science 309:2226–2228PubMedCrossRefGoogle Scholar
  53. 53.
    Vassal M, Le Bars E, Moritz-Gasser S, Menjot N, Duffau H (2010) Crossed aphasia elicited by intraoperative cortical and subcortical stimulation in awake patients. J Neurosurg 113:1251–1258PubMedCrossRefGoogle Scholar
  54. 54.
    Vigneau M, Beaucousin V, Herve PY, Duffau H, Crivello F, Houdé O, Mazoyer B, Tzourio-Mazoyer N (2006) Meta-analyzing left hemisphere language areas: phonology, semantics, and sentence processing. Neuroimage 30:1414–1432PubMedCrossRefGoogle Scholar
  55. 55.
    Yordanova YN, Moritz-Gasser S, Duffau H (2011) Awake surgery for WHO grade II gliomas within “noneloquent” areas in the left dominant hemisphere: toward a “supratotal” resection. J Neurosurg 115:232–239PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  1. 1.Department of Neurosurgery, Hôpital Gui de ChauliacMontpellier University Medical CenterMontpellierFrance
  2. 2.Institute for Neuroscience of Montpellier, INSERM U1051, Team “Plasticity of Central Nervous System, Human Stem Cells and Glial Tumors”Hôpital Saint Eloi, CHU MontpellierMontpellierFrance

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