The diagnostic value of contrast enhancement on MRI in diffuse and anaplastic gliomas

Acta Neurochirurgica (2022) 164:2035–2040

We evaluated differentiations in gadolinium contrast enhancement (CE) between low-grade WHO °II and high-grade WHO °III gliomas in conventional MRI, which have been repeatedly questioned.

Methods Ninety-nine patients, who underwent first resection of WHO°II and °III gliomas, were retrospectively retrieved from a prospective database. The quantitative metric volume of Gd-CE in T1-weighted pre-operative MRI was measured using volumetric segmentation.

Results The OR to detect CE in anaplastic gliomas was seven times higher than that in diffuse gliomas (CI95% 2.817.2, p<0.0001). No CE was seen in 50% (8/16) of focal anaplastic and in 28% (10/36) of entirely anaplastic gliomas. CE was present in 21% (10/47) of diffuse gliomas. Anaplasia correlated with a larger CE volume (r=0.49, p<0.0001) and provided additional 4 cm 3 of CE volume compared to entirely diffuse tumors. The OR to have CE was 3.6 times for IDH1 wild-type tumors (CI95% 1.3–10.2, p=0.05) and 4.8 for tumors with ATRX expression (CI95% 1.3–17.2, p=0.05). In all sub-groups, at least a quarter of cases showed no CE at all and there were cases with present CE.

Conclusion CE is associated with higher odds of unfavorable prognostic features like anaplasia, wild-type IDH1 and retained ATRX. There was no CE in one-fourth of anaplastic gliomas and half of gliomas with focal anaplasia.

Surgery of Insular Diffuse Gliomas—Part 2: Probabilistic Cortico-Subcortical Atlas of Critical Eloquent Brain Structures and Probabilistic Resection Map During Transcortical Awake Resection

Neurosurgery 89:579–590, 2021

Insular diffuse glioma surgery is challenging, and tools to help surgical planning could improve the benefit-to-risk ratio.

OBJECTIVE: To provide a probabilistic resection map and frequency atlases of critical eloquent regions of insular diffuse gliomas based on our surgical experience.

METHODS: We computed cortico-subcortical “eloquent” anatomic sites identified intraoperatively by direct electrical stimulations during transcortical awake resection of insular diffuse gliomas in adults.

RESULTS: From 61 insular diffuse gliomas (39 left, 22 right; all left hemispheric dominance for language), we provided a frequency atlas of eloquence of the opercula (left/right; pars orbitalis: 0%/5.0%; pars triangularis: l5.6%/4.5%; pars opercularis: 37.8%/27.3%; precentral gyrus: 97.3%/95.4%; postcentral and supramarginal gyri: 75.0%/57.1%; temporal pole and superior temporal gyrus: 13.3%/0%), which tailored the transcortical approach (frontal operculum to reach the antero-superior insula, temporal operculum to reach the inferior insula, parietal operculum to reach the posterior insula). We provided a frequency atlas of eloquence identifying the subcortical functional boundaries (36.1% pyramidal pathways, 50.8% inferior fronto-occipital fasciculus, 13.1% arcuate and superior longitudinal fasciculi complex, 3.3% somatosensory pathways, 8.2% caudate and lentiform nuclei). Vascular boundaries and increasing errors during testing limited the resection in 8.2% and 11.5% of cases, respectively. We provided a probabilistic 3-dimensional atlas of resectability.

CONCLUSION: Functional mapping under awake conditions has to be performed intraoperatively in each patient to guide surgical approach and resection of insular diffuse gliomas in right and left hemispheres. Frequency atlases of opercula eloquence and of subcortical eloquent anatomic boundaries, and probabilistic 3-dimensional atlas of resectability could guide neurosurgeons.

Surgery of Insular Diffuse Gliomas—Part 1: Transcortical Awake Resection Is Safe and Independently Improves Overall Survival

Neurosurgery 89:565–578, 2021

Insular diffuse glioma resection is at risk of vascular injury and of postoperative new neurocognitive deficits.

OBJECTIVE: To assess safety and efficacy of surgical management of insular diffuse gliomas.

METHODS: Observational, retrospective, single-institution cohort analysis (2005-2019) of 149 adult patients surgically treated for an insular diffuse glioma: transcortical awake resection with intraoperative functional mapping (awake resection subgroup, n = 61), transcortical asleep resection without functional mapping (asleep resection subgroup, n = 50), and stereotactic biopsy (biopsy subgroup, n = 38). All cases were histopathologically assessed according to the 2016World Health Organization classification and cIMPACTNOW update 3.

RESULTS: Following awake resection, 3/61 patients had permanent motor deficit, seizure control rates improved (89% vs 69% preoperatively, P = .034), and neurocognitive performance improved from 5% to 24% in tested domains, despite adjuvant oncological treatments. Resection rates were higher in the awake resection subgroup (median 94%) than in the asleep resection subgroup (median 46%; P < .001). There was more gross total resection (25% vs 12%) and less partial resection (34% vs 80%) in the awake resection subgroup than in the asleep resection subgroup (P< .001). Karnofsky Performance Status score <70 (adjusted hazard ratio [aHR] 2.74, P = .031), awake resection (aHR 0.21, P = .031), isocitrate dehydrogenase (IDH)-mutant grade 2 astrocytoma (aHR 5.17, P = .003), IDHmutant grade 3 astrocytoma (aHR 6.11, P < .001), IDH-mutant grade 4 astrocytoma (aHR 13.36, P = .008), and IDH-wild-type glioblastoma (aHR 21.84, P < .001) were independent predictors of overall survival.

CONCLUSION:Awake surgery preserving the brain connectivity is safe, allows larger resections for insular diffuse gliomas than asleep resection, and positively impacts overall survival.

Intraoperative Cognition Mapping and Monitoring “à la carte” in Brain Tumor Patients

Neurosurgery 88:919–930, 2021

The purpose of surgery for brain tumors involving eloquent neural circuits is to maximize the extent of resection while preserving an optimal quality of life. To this end, especially in diffuse glioma, the goal is to remove the cerebral parenchyma invaded by the neoplasm up to the individual cortico-subcortical networks critical for brain functions.

Intraoperative mapping combined with real-time cognitive monitoring throughout the resection in awake patient is thus highly recommended to resume a normal life. Indeed, beyond avoiding hemiplegia or aphasia, enjoying a familial, social, and professional life implies that motor and language mapping is not sufficient.

Identifying and sparing neural networks that subserve cognition (movement control, visuospatial cognition, executive functions, multimodal semantics, metacognition) andmentalizing (theory ofmind, which plays a key role for social cognition) is essential to preserve an adapted behavior.

Here, the aim is to review when and how to map these critical functions, which have nonetheless been neglected for many decades by neurosurgeons. In fact, the disorders generated by surgical injuries of circuits underpinning nonmotor and nonspeech functions are usually not immediately visible on postoperative standard clinical examination, leading the physician to believe that the patient has no deficit. Yet, cognitive or emotional disturbances may subsequently prevent to resume an active life, as to work full time.

Therefore, a systematic neuropsychological assessment should be performed before, during, and after mapping-guided surgery, regardless of the tumor location, to preserve the functional connectome intraoperatively and to plan a postoperative tailored cognitive rehabilitation according to the patient’s needs.

Altered Motor Excitability in Patients With Diffuse Gliomas Involving Motor Eloquent Areas: The Impact of Tumor Grading

Neurosurgery 88( 1) 2021: 183–192

Diffuse gliomas have an increased biological aggressiveness across the World Health Organization (WHO) grading system. The implications of glioma grading on the primary motor cortex (M1)-corticospinal tract (CST) excitability is unknown.

OBJECTIVE: To assess the excitability of the motor pathway with navigated transcranial magnetic stimulation (nTMS).

METHODS: Retrospective cohort study of patients admitted for surgery with diffuse gliomas within motor eloquent areas. Demographic, clinical, and nTMS-related variables were collected. The Cortical Excitability Score (CES 0 to 2 according to the number of abnormal interhemispheric resting motor threshold (RMT) ratios) was calculated for patients where bilateral upper and lower limb mapping was performed.

RESULTS: A total of 45 patients were included: 9 patients had a low-grade glioma and 36 patients had a high-grade glioma. The unadjusted analysis revealed an increase in the latency of the motor evoked potential of the lower limb with an increase of theWHOgrade (P = .038). The adjusted analysis confirmed this finding (P = .013) and showed a relation between the increase in the WHO and a decreased RMT (P = .037) of the motor evoked responses in the lower limb.When CES was calculated, an increase in the score was related with an increase in the WHO grade (unadjusted analysis—P = .0001; adjusted analysis— P = .001) and in isocitrate dehydrogenase (IDH) wild-type tumors (unadjusted analysis— P = .020).

CONCLUSION: An increase in the WHO grading system and IDH wild-type tumors are associated with an abnormal excitability of the motor eloquent areas in patients with diffuse gliomas.

Iterative Surgical Resections of Diffuse Glioma With Awake Mapping: How to Deal With Cortical Plasticity and Connectomal Constraints?

Neurosurgery 85(1):105–116. 2019

In diffuse glioma, a multistage approach with iterative tailored surgical resections can be considered.
OBJECTIVE: To compare results of iterative intrasurgical brain mappings to investigate the potential and limitation of neuroplasticity at the individual stage, and to highlight to what extent it can influence the therapeutic strategy.
METHODS: Glioma patients who underwent 2 consecutive awake surgeries with cortical and subcortical stimulation were classified into group 1 (n = 23) if cortical mappings exhibited high level of plasticity (displacement of ≥2 sites) or into group 2 (n = 19) with low level of plasticity.
RESULTS: Clinical characteristics did not differ significantly between both groups. The borders of the tumors were mostly sharp in group 1 (82.6%) and rather indistinct in group 2 (84.2%), (P = .00001). Tumor remnants were more often cortical (± subcortical) in group 1 (39.1%) and more often purely subcortical in group 2 (68.4%; P = .009). In group 1, the time needed to recover independence was significantly shorter at reoperation (37.6 h vs 78.3 h after the first surgery, P = .00003) while this difference was not significant in group 2. The iterative extents of resection (EOR) remain comparable in group 1 (94% vs 92%, P = .40) but were significantly smaller in group 2 at reoperation (94% vs 88%, P = .05).
CONCLUSION: More efficient plasticity mechanisms are facilitated by cortical tumors with sharp borders, are associated with an increase of EOR at reoperation and with earlier functional recovery. Tumoral invasion of the white matter tracts represents the main limitation of neuroplasticity: this connectomal constraint limits EOR during second surgery.