Journal of Neuro-Oncology

, Volume 141, Issue 1, pp 167–182 | Cite as

Effects of surgery on neurocognitive function in patients with glioma: a meta-analysis of immediate post-operative and long-term follow-up neurocognitive outcomes

  • Justin Choon Hwee Ng
  • Angela An Qi See
  • Ting Yao Ang
  • Lysia Yan Rong Tan
  • Beng Ti Ang
  • Nicolas Kon Kam KingEmail author
Clinical Study



This study aims to identify the neuropsychological tests commonly used for assessment in each neurocognitive domain, and quantify the post-operative changes in neurocognitive function in the immediate post-operation and follow-up.


With the use of the PubMed, a comprehensive search of the English literature was performed following PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. There were 1021 publications identified for screening. Standardized mean differences (SMD) in neuropsychological task performance were calculated both for immediate post-operation (up to 1 week) and follow-up (up to 6 months).


Out of 12 studies which met the inclusion criteria, 11 studies were analyzed in this meta-analysis, with a total of 313 patients (age range 18–82, 50% males) with intracranial gliomas (45% high-grade, 55% low-grade). Complex attention, language and executive function were the most frequently tested neurocognitive domains. Surgery had a positive impact in the domains of complex attention, language, learning and memory tasks in the immediate post-operative period and sustained improvement at follow-up. In contrast, surgery was found to negatively impact performance for executive function in the immediate post-operative period with sustained decline in performance in the long term.


This meta-analysis suggests that surgery for glioma confers a benefit for the domains of complex attention, language, learning and memory, while negatively affecting executive function, in the periods immediately after surgery and at 6 months follow-up. In addition, awake surgery seemed to confer a beneficial effect on neurocognitive functions. Future research should attempt to standardize a battery of neuropsychological tests for patients undergoing surgical resection for glioma, perhaps with a particular focus on executive function.


Glioma Surgical resection Neurocognitive function Adult Meta-analysis 



This research is supported by Singapore Ministry of Health’s National Medical Research Council under its Translational and Clinical Research Flagship Programme - Tier 1 (Project No: NMRC/TCR/016-NNI/2016).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors. For this type of study formal consent is not required.

Supplementary material

11060_2018_3023_MOESM1_ESM.docx (16 kb)
Supplementary material 1 (DOCX 16 KB)
11060_2018_3023_MOESM2_ESM.docx (18 kb)
Supplementary material 2 (DOCX 19 KB)


  1. 1.
    Jakola AS, Skjulsvik AJ, Myrmel KS, Sjavik K, Unsgard G, Torp SH, Aaberg K, Berg T, Dai HY, Johnsen K, Kloster R, Solheim O (2017) Surgical resection versus watchful waiting in low-grade gliomas. Ann Oncol 28(8):1942–1948. CrossRefGoogle Scholar
  2. 2.
    Brown TJ, Bota DA, Maher EA, Aregawi DG, Liau LM, Brown PD, Buckner JC, Weller M, Bent MJVD, Berger MS, Glantz MJ (2017) Association of aggressive resection with survival and progression-free survival in adult low-grade glioma: A systematic review and meta-analysis with numbers needed to treat. J Clin Oncol 35(15_suppl):2025–2025. CrossRefGoogle Scholar
  3. 3.
    Bunevicius A, Tamasauskas S, Deltuva V, Tamasauskas A, Radziunas A, Bunevicius R (2014) Predictors of health-related quality of life in neurosurgical brain tumor patients: focus on patient-centered perspective. Acta Neurochirurgica 156(2):367–374. CrossRefGoogle Scholar
  4. 4.
    Zucchella C, Bartolo M, Di Lorenzo C, Villani V, Pace A (2013) Cognitive impairment in primary brain tumors outpatients: a prospective cross-sectional survey. Journal of Neuro Oncol 112(3):455–460. CrossRefGoogle Scholar
  5. 5.
    Hentschel SJ, Lang FF (2005) Surgical resection of intrinsic insular tumors. Neurosurgery 57(1 Suppl):176–183; discussion 176–183Google Scholar
  6. 6.
    Lang FF, Olansen NE, DeMonte F, Gokaslan ZL, Holland EC, Kalhorn C, Sawaya R (2001) Surgical resection of intrinsic insular tumors: complication avoidance. J Neurosurg 95(4):638–650. CrossRefGoogle Scholar
  7. 7.
    Neuloh G, Pechstein U, Schramm J (2007) Motor tract monitoring during insular glioma surgery. J Neurosurg 106(4):582–592. CrossRefGoogle Scholar
  8. 8.
    Sanai N, Polley MY, Berger MS (2010) Insular glioma resection: assessment of patient morbidity, survival, and tumor progression. J Neurosurg 112(1):1–9. CrossRefGoogle Scholar
  9. 9.
    Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H (2005) The montreal cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 53(4):695–699. CrossRefGoogle Scholar
  10. 10.
    Olson RA, Iverson GL, Carolan H, Parkinson M, Brooks BL, McKenzie M (2011) Prospective comparison of two cognitive screening tests: diagnostic accuracy and correlation with community integration and quality of life. J Neuro Oncol 105(2):337–344. CrossRefGoogle Scholar
  11. 11.
    Satoer D, Visch-Brink E, Dirven C, Vincent A (2016) Glioma surgery in eloquent areas: can we preserve cognition? Acta Neurochirurgica 158(1):35–50. CrossRefGoogle Scholar
  12. 12.
    Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151(4):264–269, w264CrossRefGoogle Scholar
  13. 13.
    Janulewicz PA, Krengel MH, Maule A, White RF, Cirillo J, Sisson E, Heeren T, Sullivan K (2017) Neuropsychological characteristics of Gulf War illness: a meta-analysis. PloS ONE 12(5):e0177121. CrossRefGoogle Scholar
  14. 14.
    Cohen J (1988) Statistical power analysis for the behavioral sciences. 2nd edn., New York University, New YorkGoogle Scholar
  15. 15.
    Abrams KR, Gillies CL, Lambert PC (2005) Meta-analysis of heterogeneously reported trials assessing change from baseline. Stat Med 24(24):3823–3844. CrossRefGoogle Scholar
  16. 16.
    Borenstein M, Hedges LV, Higgins JP, Rothstein HR (2011) Introduction to meta-analysis. Wiley, HobokenGoogle Scholar
  17. 17.
    Higgins JP, Green S (2011) Cochrane handbook for systematic reviews of interventions, vol 4. Wiley, HobokenGoogle Scholar
  18. 18.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560. CrossRefGoogle Scholar
  19. 19.
    Dickersin K, Berlin JA (1992) Meta-analysis: state-of-the-science. Epidemiol Rev 14:154–176CrossRefGoogle Scholar
  20. 20.
    Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558. CrossRefGoogle Scholar
  21. 21.
    Lu J, Wu J, Yao C, Zhuang D, Qiu T, Hu X, Zhang J, Gong X, Liang W, Mao Y, Zhou L (2013) Awake language mapping and 3-Tesla intraoperative MRI-guided volumetric resection for gliomas in language areas. J Clin Neurosci 20(9):1280–1287. CrossRefGoogle Scholar
  22. 22.
    Bello L, Gallucci M, Fava M, Carrabba G, Giussani C, Acerbi F, Baratta P, Songa V, Conte V, Branca V, Stocchetti N, Papagno C, Gaini SM (2007) Intraoperative subcortical language tract mapping guides surgical removal of gliomas involving speech areas. Neurosurgery 60(1):67–80. discussion 80–62.CrossRefGoogle Scholar
  23. 23.
    Braun V, Albrecht A, Kretschmer T, Richter HP, Wunderlich A (2006) Brain tumour surgery in the vicinity of short-term memory representation–results of neuronavigation using fMRI images. Acta Neurochirurgica 148(7):733–739. CrossRefGoogle Scholar
  24. 24.
    Bryszewski B, Tybor K, Ormezowska EA, Jaskolski DJ, Majos A (2013) Rearrangement of motor centers and its relationship to the neurological status of low-grade glioma examined on pre- and postoperative fMRI. Clin Neurol Neurosurg 115(12):2464–2470. CrossRefGoogle Scholar
  25. 25.
    Charras P, Herbet G, Deverdun J, de Champfleur NM, Duffau H, Bartolomeo P, Bonnetblanc F (2015) Functional reorganization of the attentional networks in low-grade glioma patients: a longitudinal study. Cortex 63:27–41. CrossRefGoogle Scholar
  26. 26.
    Herbet G, Lafargue G, Bonnetblanc F, Moritz-Gasser S, Duffau H (2013) Is the right frontal cortex really crucial in the mentalizing network? A longitudinal study in patients with a slow-growing lesion. Cortex 49(10):2711–2727. CrossRefGoogle Scholar
  27. 27.
    Santini B, Talacchi A, Squintani G, Casagrande F, Capasso R, Miceli G (2012) Cognitive outcome after awake surgery for tumors in language areas. J Neuro Oncol 108(2):319–326. CrossRefGoogle Scholar
  28. 28.
    Talacchi A, Santini B, Savazzi S, Gerosa M (2011) Cognitive effects of tumour and surgical treatment in glioma patients. J Neuro Oncol 103(3):541–549. CrossRefGoogle Scholar
  29. 29.
    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 Neuro Oncol 81(3):305–313. CrossRefGoogle Scholar
  30. 30.
    Whittle IR, Pringle A-M, Taylor R (1998) Effects of resective surgery for left-sided intracranial tumours on language function: a prospective study. Lancet 351(9108):1014–1018. CrossRefGoogle Scholar
  31. 31.
    Wolf J, Campos B, Bruckner T, Vogt L, Unterberg A, Ahmadi R (2016) Evaluation of neuropsychological outcome and “quality of life” after glioma surgery. Langenbecks Arch Surg 401(4):541–549. CrossRefGoogle Scholar
  32. 32.
    Papagno C, Miracapillo C, Casarotti A, Romero Lauro LJ, Castellano A, Falini A, Casaceli G, Fava E, Bello L (2011) What is the role of the uncinate fasciculus? Surgical removal and proper name retrieval. Brain 134(Pt 2):405–414. CrossRefGoogle Scholar
  33. 33.
    Barzilai O, Ben Moshe S, Sitt R, Sela G, Shofty B, Ram Z (2018) Improvement in cognitive function after surgery for low-grade glioma. J Neurosurg 23:1–9CrossRefGoogle Scholar
  34. 34.
    Duffau H, Capelle L, Denvil D, Sichez N, Gatignol P, Taillandier L, Lopes M, Mitchell MC, Roche S, Muller JC, Bitar A (2003) Usefulness of intraoperative electrical subcortical mapping during surgery for low-grade gliomas located within eloquent brain regions: functional results in a consecutive series of 103 patients. J Neurosurg 98(4):764–778. CrossRefGoogle Scholar
  35. 35.
    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(3):461–471. CrossRefGoogle Scholar
  36. 36.
    Scheibel RS, Meyers CA, Levin VA (1996) Cognitive dysfunction following surgery for intracerebral glioma: influence of histopathology, lesion location, and treatment. J Neurooncol 30(1):61–69CrossRefGoogle Scholar
  37. 37.
    Campanella F, Fabbro F, Ius T, Shallice T, Skrap M (2015) Acute effects of surgery on emotion and personality of brain tumor patients: surgery impact, histological aspects, and recovery. Neuro Oncol 17(8):1121–1131CrossRefGoogle Scholar
  38. 38.
    Schiffbauer H, Ferrari P, Rowley HA, Berger MS, Roberts TP (2001) Functional activity within brain tumors: a magnetic source imaging study. Neurosurgery 49(6):1313–1321CrossRefGoogle Scholar
  39. 39.
    Atlas SW, Howard RSII, Maldjian J, Alsop D, Detre JA, Listerud J, D’Esposito M, Judy KD, Zager E, Stecker M (1996) Functional magnetic resonance imaging of regional brain activity in patients with intracerebral gliomas: findings and implications for clinical management. Neurosurgery 38(2):329–338CrossRefGoogle Scholar
  40. 40.
    Desmurget M, Bonnetblanc F, Duffau H (2007) Contrasting acute and slow-growing lesions: a new door to brain plasticity. Brain 130(4):898–914. CrossRefGoogle Scholar
  41. 41.
    Bosma I, Vos MJ, Heimans JJ, Taphoorn MJ, Aaronson NK, Postma TJ, van der Ploeg HM, Muller M, Vandertop WP, Slotman BJ, Klein M (2007) The course of neurocognitive functioning in high-grade glioma patients. Neuro Oncol 9(1):53–62. CrossRefGoogle Scholar
  42. 42.
    Kayl AE, Meyers CA (2003) Does brain tumor histology influence cognitive function? Neuro Oncol 5(4):255–260. CrossRefGoogle Scholar
  43. 43.
    Satoer D, Vork J, Visch-Brink E, Smits M, Dirven C, Vincent A (2012) Cognitive functioning early after surgery of gliomas in eloquent areas. J Neurosurg 117(5):831–838. CrossRefGoogle Scholar
  44. 44.
    De Witt Hamer PC1, Robles SG, Zwinderman AH, Duffau H, Berger MS (2012) Impact of intraoperative stimulation brain mapping on glioma surgery outcome: a meta-analysis. J Clin Oncol 30(20):2559–2565. CrossRefGoogle Scholar
  45. 45.
    Lu VM, Phan K, Rovin RA (2018) Comparison of operative outcomes of eloquent glioma resection performed under awake versus general anesthesia: a systematic review and meta-analysis. Clin Neurol Neurosurg 169:121–127. CrossRefGoogle Scholar
  46. 46.
    Talacchi A, Santini B, Casartelli M, Monti A, Capasso R, Miceli G (2013) Awake surgery between art and science. part II: language and cognitive mapping. Funct Neurol 28(3):223–239. Google Scholar
  47. 47.
    Wager M, Du Boisgueheneuc F, Pluchon C, Bouyer C, Stal V, Bataille B, Guillevin CM, Gil R (2013) Intraoperative monitoring of an aspect of executive functions. Oper Neurosurg 72:ons169–ons180. (2 Suppl Operative)CrossRefGoogle Scholar
  48. 48.
    Norman DA, Shallice T (1986) Attention to Action. In: Davidson RJ, Schwartz GE, Shapiro D (eds) Consciousness and self-regulation: advances in research and theory volume 4. Springer, Boston, pp 1–18. Google Scholar
  49. 49.
    Kaleita TA, Wellisch DK, Cloughesy TF, Ford JM, Freeman D, Belin TR, Goldman J (2004) Prediction of neurocognitive outcome in adult brain tumor patients. J Neuro Oncol 67(1–2):245–253CrossRefGoogle Scholar
  50. 50.
    Taphoorn MJ, Klein M (2004) Cognitive deficits in adult patients with brain tumours. Lancet Neurol 3(3):159–168. CrossRefGoogle Scholar
  51. 51.
    Sarubbo S, Latini F, Panajia A, Candela C, Quatrale R, Milani P, Fainardi E, Granieri E, Trapella G, Tugnoli V, Cavallo MA (2011) Awake surgery in low-grade gliomas harboring eloquent areas: 3-year mean follow-up. Neurol Sci 32(5):801–810. CrossRefGoogle Scholar
  52. 52.
    Gehring K, Sitskoorn MM, Gundy CM, Sikkes SA, Klein M, Postma TJ, van den Bent MJ, Beute GN, Enting RH, Kappelle AC, Boogerd W (2009) Cognitive rehabilitation in patients with gliomas: a randomized, controlled trial. J Clin Oncol 27(22):3712–3722. CrossRefGoogle Scholar
  53. 53.
    Zucchella C, Capone A, Codella V, De Nunzio AM, Vecchione C, Sandrini G, Pace A, Pierelli F, Bartolo M (2013) Cognitive rehabilitation for early post-surgery inpatients affected by primary brain tumor: a randomized, controlled trial. J Neurooncol 114(1):93–100. CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
  2. 2.Department of NeurosurgerySingapore General HospitalSingaporeSingapore
  3. 3.Department of NeurosurgeryNational Neuroscience InstituteSingaporeSingapore
  4. 4.Duke-NUS Medical SchoolSingaporeSingapore

Personalised recommendations