Executive functioning following surgery near the frontal aslant tract in low-grade glioma patients: A patient-specific tractography study.

BACKGROUND: The Frontal Aslant Tract (FAT) has been associated with executive functions (EF), but it remains unclear what role the FAT plays in EF, and whether preoperative dysfunction of the FAT is associated to long-lasting postsurgical executive impairments. METHODS: In this study, we examined the course of EF from pre-surgery (n = 75) to 3 (n = 61) and 12 (n = 25) months after surgery in patients with frontal and parietal low-grade gliomas (LGGs), to establish the degree to which long-term EF deficits exist. Secondly, we used patient-specific tractography to investigate the extent to which overlap of the tumor with the FAT, as well as integrity of the FAT, presurgery were related to EF on the short and longer term after surgery. RESULTS: LGG patients performed worse than healthy controls on all EF tests before and 3 months postsurgery. Whereas performances on three out of the four tests had normalized 1 year postsurgery (n = 26), performance on the cognitive flexibility test remained significantly worse than in healthy controls. Patients in whom the tumor overlapped with the core of the right FAT performed worse presurgery on three of the EF tests compared to those in whom the tumor did not overlap with the right FAT. Presurgical right FAT integrity was not related to presurgical EF, but only to postsurgical EF (from pre-to 3 months postsurgery). Longitudinal analyses demonstrated that patients with right (but not left) FAT core overlap performed on average worse over the pre- and postsurgical timepoints on the cognitive flexibility test. CONCLUSIONS: We emphasized that LGG patients perform worse than healthy controls on the EF tests, which normalizes 1-year postsurgery except for cognitive flexibility. Importantly, in patients with right hemispheric tumors, tumor involvement of the FAT was associated with worse pre- and 3- months postsurgical performance, specifically concerning cognitive flexibility.

Characterization and Classification of Spatial White Matter Tract Alteration Patterns in Glioma Patients Using Magnetic Resonance Tractography: A Systematic Review and Meta-Analysis.

INTRODUCTION: Magnetic resonance (MR) tractography can be used to study the spatial relations between gliomas and white matter (WM) tracts. Various spatial patterns of WM tract alterations have been described in the literature. We reviewed classification systems of these patterns, and investigated whether low-grade gliomas (LGGs) and high-grade gliomas (HGGs) demonstrate distinct spatial WM tract alteration patterns. METHODS: We conducted a systematic review and meta-analysis to summarize the evidence regarding MR tractography studies that investigated spatial WM tract alteration patterns in glioma patients. RESULTS: Eleven studies were included. Overall, four spatial WM tract alteration patterns were reported in the current literature: displacement, infiltration, disruption/destruction and edematous. There was a considerable heterogeneity in the operational definitions of these terms. In a subset of studies, sufficient homogeneity in the classification systems was found to analyze pooled results for the displacement and infiltration patterns. Our meta-analyses suggested that LGGs displaced WM tracts significantly more often than HGGs (n = 259 patients, RR: 1.79, 95% CI [1.14, 2.79], I2 = 51%). No significant differences between LGGs and HGGs were found for WM tract infiltration (n = 196 patients, RR: 1.19, 95% CI [0.95, 1.50], I2 = 4%). CONCLUSIONS: The low number of included studies and their considerable methodological heterogeneity emphasize the need for a more uniform classification system to study spatial WM tract alteration patterns using MR tractography. This review provides a first step towards such a classification system, by showing that the current literature is inconclusive and that the ability of fractional anisotropy (FA) to define spatial WM tract alteration patterns should be critically evaluated. We found variations in spatial WM tract alteration patterns between LGGs and HGGs, when specifically examining displacement and infiltration in a subset of the included studies.

Presurgical Executive Functioning in Low-Grade Glioma Patients Cannot Be Topographically Mapped.

Executive dysfunctions have a high prevalence in low-grade glioma patients and may be the result of structural disconnections of particular subcortical tracts and/or networks. However, little research has focused on preoperative low-grade glioma patients. The frontotemporoparietal network has been closely linked to executive functions and is substantiated by the superior longitudinal fasciculus. The aim of this study was to investigate their role in executive functions in low-grade glioma patients. Patients from two neurological centers were included with IDH-mutated low-grade gliomas. The sets of preoperative predictors were (i) distance between the tumor and superior longitudinal fasciculus, (ii) structural integrity of the superior longitudinal fasciculus, (iii) overlap between tumor and cortical networks, and (iv) white matter disconnection of the same networks. Linear regression and random forest analyses were performed. The group of 156 patients demonstrated significantly lower performance than normative samples and had a higher prevalence of executive impairments. However, both regression and random forest analyses did not demonstrate significant results, meaning that neither structural, cortical network overlap, nor network disconnection predictors explained executive performance. Overall, our null results indicate that there is no straightforward topographical explanation of executive performance in low-grade glioma patients. We extensively discuss possible explanations, including plasticity-induced network-level equipotentiality. Finally, we stress the need for the development of novel methods to unveil the complex and interacting mechanisms that cause executive deficits in low-grade glioma patients.

A systematic review of the use of subcortical intraoperative electrical stimulation mapping for monitoring of executive deficits and neglect: what is the evidence so far?

BACKGROUND: Over the past decade, the functional importance of white matter pathways has been increasingly acknowledged in neurosurgical planning. A method to directly study anatomo-functional correlations is direct electrical stimulation (DES). DES has been widely accepted by neurosurgeons as a reliable tool to minimize the occurrence of permanent postoperative motor, vision, and language deficits. In recent years, DES has also been used for stimulation mapping of other cognitive functions, such as executive functions and visuospatial awareness. METHODS: The aim of this review is to summarize the evidence so far from DES studies on subcortical pathways that are involved in visuospatial awareness and in the following three executive functions: (1) inhibitory control, (2) working memory, and (3) cognitive flexibility. RESULTS: Eleven articles reported on intraoperative electrical stimulation of white matter pathways to map the cognitive functions and explicitly clarified which subcortical tract was stimulated. The results indicate that the right SLF-II is involved in visuospatial awareness, the left SLF-III and possibly the right SLF-I are involved in working memory, and the cingulum is involved in cognitive flexibility. CONCLUSIONS: We were unable to draw any more specific conclusions, nor unequivocally establish the critical involvement of pathways in executive functions or visuospatial awareness due to the heterogeneity of the study types and methods, and the limited number of studies that assessed these relationships. Possible approaches for future research to obtain converging and more definite evidence for the involvement of pathways in specific cognitive functions are discussed.

The frontal aslant tract and its role in executive functions: a quantitative tractography study in glioma patients.

Focal white matter lesions can cause cognitive impairments due to disconnections within or between networks. There is some preliminary evidence that there are specific hubs and fiber pathways that should be spared during surgery to retain cognitive performance. A tract potentially involved in important higher-level cognitive processes is the frontal aslant tract. It roughly connects the posterior parts of the inferior frontal gyrus and the superior frontal gyrus. Functionally, the left frontal aslant tract has been associated with speech and the right tract with executive functions. However, there currently is insufficient knowledge about the right frontal aslant tract's exact functional importance. The aim of this study was to investigate the role of the right frontal aslant tract in executive functions via a lesion-symptom approach. We retrospectively examined 72 patients with frontal glial tumors and correlated measures from tractography (distance between tract and tumor, and structural integrity of the tract) with cognitive test performances. The results indicated involvement of the right frontal aslant tract in shifting attention and letter fluency. This involvement was not found for the left tract. Although this study was exploratory, these converging findings contribute to a better understanding of the functional frontal subcortical anatomy. Shifting attention and letter fluency are important for healthy cognitive functioning, and when impaired they may greatly influence a patient's wellbeing. Further research is needed to assess whether or not damage to the right frontal aslant tract causes permanent cognitive impairments, and consequently identifies this tract as a critical pathway that should be taken into account during neurosurgical procedures.

Executive functional deficits during electrical stimulation of the right frontal aslant tract.

Direct electrical stimulation mapping was used to map executive functions during awake surgery of a patient with a right frontal low-grade glioma. We specifically targeted the frontal aslant tract, as this pathway had been infiltrated by the tumor. The right frontal aslant tract has been implicated in executive functions in the neuroscientific literature, but is yet of unknown relevance for clinical practice. Guided by tractography, electrical stimulation of the frontal aslant tract disrupted working memory and inhibitory functions. In this report we illustrate the dilemmas that neurosurgeons face when balancing maximal tumor resection against optimal cognitive performance. In particular, we emphasize that intraoperative tasks that target cognitive functions should be carefully introduced in clinical practice to prevent clinically irrelevant responses and too early termination of the resection.

Effect of frailty on quality of life in elderly patients after hip fracture: a longitudinal study.

OBJECTIVES: The aims of this study were to examine the pattern of changes over time in health status (HS) and quality of life (QoL) in the first year after hip fracture and to quantify the association between frailty at the onset of hip fracture and the change in HS and QoL 1 year later. The major hypothesis was that frailty, a clinical state of increased vulnerability, is a good predictor of QoL in patients recovering from hip fracture. DESIGN: Prospective, observational, follow-up cohort study. SETTING: Secondary care. Ten participating centres in Brabant, the Netherlands. PARTICIPANTS: 1091 patients entered the study and 696 patients completed the study. Patients with a hip fracture aged 65 years and older or proxy respondents for patients with cognitive impairment were included in this study. MAIN OUTCOME MEASURES: The primary outcomes were HS (EuroQol-5 Dimensions questionnaire) and capability well-being (ICEpop CAPability measure for Older people). Prefracture frailty was defined with the Groningen Frailty Indicator (GFI), with GFI ≥4 indicating frailty. Participants were followed up at 1 month, 3 months, 6 months and 1 year after hospital admission. RESULTS: In total, 371 patients (53.3%) were considered frail. Frailty was negatively associated with HS (ß -0.333; 95% CI -0.366 to -0.299), self-rated health (ß -21.9; 95% CI -24.2 to -19.6) and capability well-being (ß -0.296; 95% CI -0.322 to -0.270) in elderly patients 1 year after hip fracture. After adjusting for confounders, including death, prefracture HS, age, prefracture residential status, prefracture mobility, American Society of Anesthesiologists grading and dementia, associations were weakened but remained significant. CONCLUSIONS: We revealed that frailty is negatively associated with QoL 1 year after hip fracture, even after adjusting for confounders. This finding suggests that early identification of prefracture frailty in patients with a hip fracture is important for prognostic counselling, care planning and the tailoring of treatment. TRIAL REGISTRATION NUMBER: NCT02508675.