Improvement in cognitive function after surgery for low-grade glioma

Restricted access


Cognition is a key component in health-related quality of life (HRQoL) and is currently incorporated as a major parameter of outcome assessment in patients treated for brain tumors. The effect of surgery on cognition and HRQoL remains debatable. The authors investigated the impact of resection of low-grade gliomas (LGGs) on cognition and the correlation with various histopathological markers.


A retrospective analysis of patients with LGG who underwent craniotomy for tumor resection at a single institution between 2010 and 2014 was conducted. Of 192 who underwent resective surgery for LGG during this period, 49 had complete pre- and postoperative neurocognitive evaluations and were included in the analysis. These patients completed a full battery of neurocognitive tests (memory, language, attention and working memory, visuomotor organization, and executive functions) pre- and postoperatively. Tumor and surgical characteristics were analyzed, including volumetric measurements and histopathological markers (IDH, p53, GFAP).


Postoperatively, significant improvement was found in memory and executive functions. A subgroup analysis of patients with dominant-side tumors, most of whom underwent intraoperative awake mapping, revealed significant improvement in the same domains. Patients whose tumors were on the nondominant side displayed significant improvement only in memory functions. Positive staining for p53 testing was associated with improved language function and greater extent of resection in dominant-side tumors. GFAP positivity was associated with improved memory in patients whose tumors were on the nondominant side. No correlation was found between cognitive outcome and preoperative tumor volume, residual volume, extent of resection, or IDH1 status.


Resection of LGG significantly improves memory and executive function and thus is likely to improve functional outcome in addition to providing oncological benefit. GFAP and pP53 positivity could possibly be associated with improved cognitive outcome. These data support early, aggressive, surgical treatment of LGG.

ABBREVIATIONS EOR = extent of tumor resection; fMRI = functional MRI; FWE = family-wise error; HRQoL = health-related quality of life; LGG = low-grade glioma.

Article Information

Correspondence Zvi Ram: Tel Aviv Medical Center, Tel Aviv, Israel.

INCLUDE WHEN CITING Published online March 23, 2018; DOI: 10.3171/2017.9.JNS17658.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

© AANS, except where prohibited by US copyright law.



  • View in gallery

    Representation of tumor locations. Tumors are grouped according to their anatomical location and are presented on a generic brain (fsaverage5) surface representation imported from FreeSurfer ( LH = left hemisphere; RH = right hemisphere.

  • View in gallery

    Preoperative (light gray) and postoperative (dark gray) mean cognitive scores in LGG patients. A: Mixed cohort of patients with tumors in the dominant and nondominant side. B: Patients with dominant-side tumors. C: Patients with tumors in the nondominant side. D: Patients with tumors in the left frontal lobe. The expected population average score is 0 for each test. *p < 0.05.



Aaronson NKTaphoorn MJHeimans JJPostma TJGundy CMBeute GN: Compromised health-related quality of life in patients with low-grade glioma. J Clin Oncol 29:443044352011


Bell BLin JJSeidenberg MHermann B: The neurobiology of cognitive disorders in temporal lobe epilepsy. Nat Rev Neurol 7:1541642011


Brat DJVerhaak RGAldape KDYung WKSalama SRCooper LA: Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med 372:248124982015


Bressler SLMenon V: Large-scale brain networks in cognition: emerging methods and principles. Trends Cogn Sci 14:2772902010


Chen RRavindra VMCohen ALJensen RLSalzman KLPrescot AP: Molecular features assisting in diagnosis, surgery, and treatment decision making in low-grade gliomas. Neurosurg Focus 38(3):E22015


Daniels TBBrown PDFelten SJWu WBuckner JCArusell RM: Validation of EORTC prognostic factors for adults with low-grade glioma: a report using intergroup 86-72-51. Int J Radiat Oncol Biol Phys 81:2182242011


Dulay MFBusch RM: Prediction of neuropsychological outcome after resection of temporal and extratemporal seizure foci. Neurosurg Focus 32(3):E42012


Dulay MFBusch RMChapin JSJehi LNajm I: Executive functioning and depressed mood before and after unilateral frontal lobe resection for intractable epilepsy. Neuropsychologia 51:137013762013


Eckel-Passow JELachance DHMolinaro AMWalsh KMDecker PASicotte H: Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N Engl J Med 372:249925082015


Fang SWang YJiang T: The influence of frontal lobe tumors and surgical treatment on advanced cognitive functions. World Neurosurg 91:3403462016


Gonen TGazit TKorn AKirschner APerry DHendler T: Intra-operative multi-site stimulation: Expanding methodology for cortical brain mapping of language functions. PLoS One 12:e01807402017


Grossman RNossek ESitt RHayat DShahar TBarzilai O: Outcome of elderly patients undergoing awake-craniotomy for tumor resection. Ann Surg Oncol 20:172217282013


Hartmann CHentschel BTatagiba MSchramm JSchnell OSeidel C: Molecular markers in low-grade gliomas: predictive or prognostic? Clin Cancer Res 17:458845992011


Helmstaedter CGleissner UZentner JElger CE: Neuropsychological consequences of epilepsy surgery in frontal lobe epilepsy. Neuropsychologia 36:6816891998


Hottinger AFHegi MEBaumert BG: Current management of low-grade gliomas. Curr Opin Neurol 29:7827882016


Houillier CWang XKaloshi GMokhtari KGuillevin RLaffaire J: IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas. Neurology 75:156015662010


Ivnik RJSharbrough FWLaws ER Jr: Effects of anterior temporal lobectomy on cognitive function. J Clin Psychol 43:1281371987


Jakola ASMyrmel KSKloster RTorp SHLindal SUnsgård G: Comparison of a strategy favoring early surgical resection vs a strategy favoring watchful waiting in low-grade gliomas. JAMA 308:188118882012


Johnson DRSawyer AMMeyers CAO’Neill BPWefel JS: Early measures of cognitive function predict survival in patients with newly diagnosed glioblastoma. Neuro Oncol 14:8088162012


Kavé G: Standardization and norms for a Hebrew naming test. Brain Lang 92:2042112005


Klein M: Neurocognitive functioning in adult WHO grade II gliomas: impact of old and new treatment modalities. Neuro Oncol 14 (Suppl 4):iv17iv242012


Klein MDuffau HDe Witt Hamer PC: Cognition and resective surgery for diffuse infiltrative glioma: an overview. J Neurooncol 108:3093182012


Klein MHeimans JJAaronson NKvan der Ploeg HMGrit JMuller M: Effect of radiotherapy and other treatment-related factors on mid-term to long-term cognitive sequelae in low-grade gliomas: a comparative study. Lancet 360:136113682002


Levidou GEl-Habr ESaetta AABamias CKatsouyanni KPatsouris E: P53 immunoexpression as a prognostic marker for human astrocytomas: a meta-analysis and review of the literature. J Neurooncol 100:3633712010 (Erratum in J Neurooncol 100:373 2010)


McAleer MFBrown PD: Neurocognitive function following therapy for low-grade gliomas. Semin Radiat Oncol 25:2102182015


Mesulam MM: From sensation to cognition. Brain 121:101310521998


Noll KRWeinberg JSZiu MBenveniste RJSuki DWefel JS: Neurocognitive changes associated with surgical resection of left and right temporal lobe glioma. Neurosurgery 77:7777852015


Nossek EMatot IShahar TBarzilai ORapoport YGonen T: Intraoperative seizures during awake craniotomy: incidence and consequences: analysis of 477 patients. Neurosurgery 73:1351402013


Nossek EMatot IShahar TBarzilai ORapoport YGonen T: Failed awake craniotomy: a retrospective analysis in 424 patients undergoing craniotomy for brain tumor. J Neurosurg 118:2432492013


Ohgaki HKleihues P: Genetic profile of astrocytic and oligodendroglial gliomas. Brain Tumor Pathol 28:1771832011


Pan IWFerguson SDLam S: Patient and treatment factors associated with survival among adult glioblastoma patients: a USA population-based study from 2000–2010. J Clin Neurosci 22:157515812015


Pelletier GVerhoef MJKhatri NHagen N: Quality of life in brain tumor patients: the relative contributions of depression, fatigue, emotional distress, and existential issues. J Neurooncol 57:41492002


Racine CALi JMolinaro AMButowski NBerger MS: Neurocognitive function in newly diagnosed low-grade glioma patients undergoing surgical resection with awake mapping techniques. Neurosurgery 77:3713792015


Reijneveld JCSitskoorn MMKlein MNuyen JTaphoorn MJ: Cognitive status and quality of life in patients with suspected versus proven low-grade gliomas. Neurology 56:6186232001


Ringel FPape HSabel MKrex DBock HCMisch M: Clinical benefit from resection of recurrent glioblastomas: results of a multicenter study including 503 patients with recurrent glioblastomas undergoing surgical resection. Neuro Oncol 18:961042016


Riva MBello L: Low-grade glioma management: a contemporary surgical approach. Curr Opin Oncol 26:6156212014


Sanai NBerger MS: Extent of resection influences outcomes for patients with gliomas. Rev Neurol (Paris) 167:6486542011


Sanai NChang SBerger MS: Low-grade gliomas in adults. J Neurosurg 115:9489652011


Sanai NPolley MYMcDermott MWParsa ATBerger MS: An extent of resection threshold for newly diagnosed glioblastomas. J Neurosurg 115:382011


Santini BTalacchi ASquintani GCasagrande FCapasso RMiceli G: Cognitive outcome after awake surgery for tumors in language areas. J Neurooncol 108:3193262012


Satoer DVincent ASmits MDirven CVisch-Brink E: Spontaneous speech of patients with gliomas in eloquent areas before and early after surgery. Acta Neurochir (Wien) 155:6856922013


Satoer DVisch-Brink EDirven CVincent A: Glioma surgery in eloquent areas: can we preserve cognition? Acta Neurochir (Wien) 158:35502016


Satoer DVisch-Brink ESmits MKloet ALooman CDirven C: Long-term evaluation of cognition after glioma surgery in eloquent areas. J Neurooncol 116:1531602014


Satoer DVork JVisch-Brink ESmits MDirven CVincent A: Cognitive functioning early after surgery of gliomas in eloquent areas. J Neurosurg 117:8318382012


Schwamm LHVan Dyke CKiernan RJMerrin ELMueller J: The Neurobehavioral Cognitive Status Examination: comparison with the Cognitive Capacity Screening Examination and the Mini-Mental State Examination in a neurosurgical population. Ann Intern Med 107:4864911987


Shields LBChoucair AK: Management of low-grade gliomas: a review of patient-perceived quality of life and neurocognitive outcome. World Neurosurg 82:e299e3092014


Sidhu MKStretton JWinston GPSymms MThompson PJKoepp MJ: Memory fMRI predicts verbal memory decline after anterior temporal lobe resection. Neurology 84:151215192015


Talacchi ASantini BSavazzi SGerosa M: Cognitive effects of tumour and surgical treatment in glioma patients. J Neurooncol 103:5415492011


Taphoorn MJB: Neurocognitive sequelae in the treatment of low-grade gliomas. Semin Oncol 30 (6 Suppl 19):45482003


Teixidor PGatignol PLeroy MMasuet-Aumatell CCapelle LDuffau H: Assessment of verbal working memory before and after surgery for low-grade glioma. J Neurooncol 81:3053132007


Trenerry MRMeador KJ: Predicting memory change after temporal lobectomy for epilepsy. Neurology 84:150815092015


Tucha OSmely CPreier MBecker GPaul GMLange KW: Preoperative and postoperative cognitive functioning in patients with frontal meningiomas. J Neurosurg 98:21312003


Tucha OSmely CPreier MLange KW: Cognitive deficits before treatment among patients with brain tumors. Neurosurgery 47:3243342000


Vakil EGreenstein YBlachstein H: Normative data for composite scores for children and adults derived from the Rey Auditory Verbal Learning Test. Clin Neuropsychol 24:6626772010


Vincent JLSnyder AZFox MDShannon BJAndrews JRRaichle ME: Coherent spontaneous activity identifies a hippocampal-parietal memory network. J Neurophysiol 96:351735312006


Wefel JSNoll KRRao GCahill DP: Neurocognitive function varies by IDH1 genetic mutation status in patients with malignant glioma prior to surgical resection. Neuro Oncol 18:165616632016


Wester KHugdahl K: Arachnoid cysts of the left temporal fossa: impaired preoperative cognition and postoperative improvement. J Neurol Neurosurg Psychiatry 59:2932981995


Wrensch MMcMillan AWiencke JWiemels JKelsey KPatoka J: Nonsynonymous coding single-nucleotide polymorphisms spanning the genome in relation to glioblastoma survival and age at diagnosis. Clin Cancer Res 13:1972052007


Yoshii YTominaga DSugimoto KTsuchida YHyodo AYonaha H: Cognitive function of patients with brain tumor in pre- and postoperative stage. Surg Neurol 69:51612008




All Time Past Year Past 30 Days
Abstract Views 94 94 94
Full Text Views 48 48 48
PDF Downloads 51 51 51
EPUB Downloads 0 0 0


Google Scholar