Pretreatment patient‐reported cognitive function in patients with diffuse glioma

Acta Neurochirurgica (2022) 164:703–711

Cognitive function is frequently assessed with objective neuropsychological tests, but patient-reported cognitive function is less explored. We aimed to investigate the preoperative prevalence of patient-reported cognitive impairment in patients with diffuse glioma compared to a matched reference group and explore associated factors.

Methods We included 237 patients with diffuse glioma and 474 age- and gender-matched controls from the general population. Patient-reported cognitive function was measured using the cognitive function subscale in the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. The transformed scale score (0–100) was dichotomized, with a score of ≤ 75 indicating clinically important patient-reported cognitive impairment. Factors associated with preoperative patient-reported cognitive impairment were explored in a multivariable regression analysis.

Results Cognitive impairment was reported by 49.8% of the diffuse glioma patients and by 23.4% in the age- and gendermatched reference group (p < 0.001). Patients with diffuse glioma had 3.2 times higher odds (95% CI 2.29, 4.58, p < 0.001) for patient-reported cognitive impairment compared to the matched reference group. In the multivariable analysis, large tumor volume, left tumor lateralization, and low Karnofsky Performance Status score were found to be independent predictors for preoperative patient-reported cognitive impairment.

Conclusions Our findings demonstrate that patient-reported cognitive impairment is a common symptom in patients with diffuse glioma pretreatment, especially in patients with large tumor volumes, left tumor lateralization, and low functional levels. Patient-reported cognitive function may provide important information about patients’ subjective cognitive health and disease status and may serve as a complement to or as a screening variable for subsequent objective testing.

Central Nervous System Plasticity Influences Language and Cognitive Recovery in Adult Glioma

Neurosurgery 89:539–548, 2021

Gliomas exist within the framework of complex neuronal circuitry in which network dynamics influence both tumor biology and cognition. The generalized impairment of cognition or loss of language function is a common occurrence for glioma patients.

The interface between intrinsic brain tumors such as gliomas and functional cognitive networks are poorly understood. The ability to communicate effectively is critically important for receiving oncological therapies and maintaining a high quality of life.

Although the propensity of gliomas to infiltrate cortical and subcortical structures and disrupt key anatomic language pathways is well documented, there is new evidence offering insight into the network and cellular mechanisms underpinning glioma-related aphasia and aphasia recovery.

In this review, we will outline the current understanding of the mechanisms of cognitive dysfunction and recovery, using aphasia as an illustrative model.

Clinical significance of vitamin D in idiopathic normal pressure hydrocephalus

Acta Neurochirurgica (2021) 163:1969–1977

Although recent studies show vitamin D deficiency is associated with cognitive decline, urinary incontinence, and gait instability, there has been no study on the effect of vitamin D on idiopathic normal pressure hydrocephalus (iNPH) characterized by the classic symptom triad of cognitive decline, urinary incontinence, and gait instability. We investigated the clinical significance of vitamin D in patients with iNPH.

Methods Between 2017 and 2020, 44 patients who underwent ventriculoperitoneal shunt surgery were divided into low (< 15 ng/mL) and high (≥ 15 ng/mL) vitamin D groups according to the concentration of 25(OH)D, an effective indicator of vitamin D status. They were respectively evaluated according to clinical and radiological findings.

Results The low vitamin D group (n = 24) showed lower preoperative cognition compared to the high vitamin D group (n = 20) in terms of Korean-Mini Mental Status Examination (K-MMSE) and iNPH grading scale (iNPHGS) (K-MMSE: 20.5   5.4 versus 24.0   4.5, p = 0.041; iNPHGS cognitive score: 2   0.9 versus 1   0.6, p = 0.025). And the low vitamin D group showed pre- and postoperatively more severe urinary incontinence (preoperative iNPHGS urinary score: 1   1.0 versus 0   0.9, p = 0.012; postoperative iNPHGS urinary score:1   1.0 versus 0   0.9, p = 0.014). The score of narrow high-convexity sulci for the low vitamin D group was lower (low vitamin D group: 1   0.7 versus high vitamin D group: 2   0.4, p = 0.031).

Conclusion Lower concentration of vitamin D in iNPH may be related to lower preoperative cognition, pre- and postoperative urinary incontinence, and brain morphological change.

A Neurosurgeon’s Guide to Cognitive Dysfunction in Adult Glioma

Neurosurgery 89:1–10, 2021

Cognitive decline is common among patients with low- and high-grade glioma and can significantly impact quality of life. Although cognitive outcomes have been studied after therapeutic interventions such as surgery and radiation, it is important to understand the impact of the disease process itself prior to any interventions.

Neurocognitive domains of interest in this disease context include intellectual function and premorbid ability, executive function, learning and memory, attention, language function, processing speed, visuospatial function, motor function, and emotional function.

Here, we review oncologic factors associated with more neurocognitive impairment, key neurocognitive tasks relevant to glioma patient assessment, as well as the relevance of the human neural connectome in understanding cognitive dysfunction in glioma patients.

A contextual understanding of glioma-functional network disruption and its impact on cognition is critical in the surgical management of eloquent area tumors.

Predicting Cognitive Improvement in Normal Pressure Hydrocephalus Patients Using Preoperative Neuropsychological Testing and Cerebrospinal Fluid Biomarkers

Neurosurgery 85:E662–E669, 2019

Though it is well known that normal pressure hydrocephalus (NPH) patients can cognitively improve after ventriculoperitoneal shunting (VPS), one of the major dilemmas in NPH is the ability to prospectively predict which patients will improve.

OBJECTIVE: To prospectively assess preoperative predictors of postshunt cognitive improvement.

METHODS: This was a prospective observational cohort including 52 consecutive patients with approximately 1-yr follow-up. Patients underwent neuropsychological testing at baseline, postlumbar drainage, and postshunt. Cerebrospinal fluid (CSF) biomarkers and cortical biopsies were also collected to examine their relationship with postshunt cognitive improvement.

RESULTS: Rey Auditory Verbal Learning Test-L (RAVLT-L) was the only neuropsychological test to demonstrate statistically significant improvement both postlumbar drain and postshunt. Improvement on the RAVLT-L postlumbar drain predicted improvement on the RAVLT-L postshunt. Patients with biopsies demonstrating Aβ+ Tau+ had lower ventricular CSF Aβ42 and higher lumbar CSF pTau compared to Aβ– Tau– patients. A receiver operating curve analysis using lumbar pTau predicted Aβ+ Tau+ biopsy status but was not related to neuropsychological test outcome.

CONCLUSION: The RAVLT can be a useful preoperative predictor of postoperative cognitive improvement, and thus, we recommend using the RAVLT to evaluate NPH patients. CSF biomarkers could not be related to neuropsychological test outcome. Future research in a larger patient sample will help determine the prospective utility of CSF biomarkers in the evaluation of NPH patients.


Glioma surgery in eloquent areas: can we preserve cognition?

Surgery for low-grade glioma infiltrating the central cerebral region

Acta Neurochir (2016) 158:35–50

Cognitive preservation is crucial in glioma surgery, as it is an important aspect of daily life functioning. Several studies claimed that surgery in eloquent areas is possible without causing severe cognitive damage. However, this conclusion was relatively ungrounded due to the lack of extensive neuropsychological testing in homogenous patient groups. In this study, we aimed to elucidate the short-term and long-term effects of glioma surgery on cognition by identifying all studies who conducted neuropsychological tests preoperatively and postoperatively in glioma patients.

Methods We systematically searched the electronical databases Embase, Medline OvidSP, Web of Science, PsychINFO OvidSP, PubMed, Cochrane, Google Scholar, Scirius and Proquest aimed at cognitive performance in glioma patients preoperatively and postoperatively.

Results We included 17 studies with tests assessing the cognitive domains: language, memory, attention, executive functions and/or visuospatial abilities. Language was the domain most frequently examined. Immediately postoperatively, all studies except one, found deterioration in one or more cognitive domains. In the longer term (3–6/6–12 months postoperatively), the following tests showed both recovery and deterioration compared with the preoperative level: naming and verbal fluency (language), verbal word learning (memory) and Trailmaking B (executive functions).

Conclusions Cognitive recovery to the preoperative level after surgery is possible to a certain extent; however, the results are too arbitrary to draw definite conclusions and not all studies investigated all cognitive domains. More studies with longer postoperative follow-up with tests for cognitive change are necessary for a better understanding of the conclusive effects of glioma surgery on cognition.

Neurocognitive Changes Associated With Surgical Resection of Left and Right Temporal Lobe Glioma

Temporal lobe tumor

Neurosurgery 77:777–785, 2015

Little is known regarding the neurocognitive impact of temporal lobe tumor resection.

OBJECTIVE: To clarify subacute surgery-related changes in neurocognitive functioning (NCF) in patients with left (LTL) and right (RTL) temporal lobe glioma.

METHODS: Patients with glioma in the LTL (n = 45) or RTL (n = 19) completed comprehensive pre- and postsurgical neuropsychological assessments. NCF was analyzed with 2-way mixed design repeated-measures analysis of variance, with hemisphere (LTL or RTL) as an independent between-subjects factor and pre- and postoperative NCF as a within-subjects factor.

RESULTS: About 60% of patients with LTL glioma and 40% with RTL lesions exhibited significant worsening on at least 1 NCF test. Domains most commonly impacted included verbal memory and executive functioning. Patients with LTL tumor showed greater decline than patients with RTL tumor on verbal memory and confrontation naming tests. Nonetheless, over one-third of patients with RTL lesions also showed verbal memory decline.

CONCLUSION: In patients with temporal lobe glioma, NCF decline in the subacute postoperative period is common. As expected, patients with LTL tumor show more frequent and severe decline than patients with RTL tumor, particularly on verbally mediated measures. However, a considerable proportion of patients with RTL tumor also exhibit decline across various domains, even those typically associated with left hemisphere structures, such as verbal memory. While patients with RTL lesions may show even greater decline in visuospatial memory, this domain was not assessed. Nonetheless, neuropsychological assessment can identify acquired deficits and help facilitate early intervention in patients with temporal lobe glioma.

Clipping of UIA and postoperative cognition

MCA aneurysm

J Neurosurg 120:937–944, 2014

The mechanisms underlying neurocognitive changes after surgical clipping of unruptured intracranial aneurysms (UIAs) are poorly understood. The aim of this study was to investigate factors that determine postoperative cognitive decline after UIA surgery.

Methods. Data from 109 patients who underwent surgical clipping of a UIA were retrospectively evaluated. These patients underwent neuropsychological examinations (NPEs), including assessment by the Wechsler Adult Intelligence Scale- Third Edition and the Wechsler Memory Scale-Revised before and 6 months after surgical clipping of the UIA. Results of NPEs were converted into z scores, from which pre- and postoperative cognitive composite scores (CSpre and CSpost) were obtained. The association between the change in CS between pre- and postoperative NPEs (that is, CSpost – CSpre [CSpost – pre]) and various variables was assessed. These latter variables included surgical approach (anterior interhemispheric approach or other approach), structural change evidenced on T2-weighted imaging at 6 months, somatosensory evoked potential amplitude decrease greater than 50% during aneurysm manipulation, preexisting multiple ischemic lesions in the lacunar region detected on preoperative T2-weighted imaging, and total microsurgical time. Paired t-tests of the NPE scores were performed to determine the net effect of these factors on neurocognitive function at 6 months.

Results. A significant CSpost – pre decrease was observed in patients with a structural change on postoperative T2-weighted imaging when compared with those without such a change on postoperative T2-weighted imaging (-0.181 vs 0.043, p = 0.012). Multiple regression analysis demonstrated that postoperative T2-weighted imaging change independently and negatively correlated with CSpost – pre (p = 0.0005). In group-rate analysis, postoperative NPE scores were significantly improved relative to preoperative scores.

Conclusions. Minimal structural damage visualized on T2-weighted images at 6 months as a result of factors such as pial/microvascular injury and excessive retraction during surgical manipulation could cause subtle but significant negative effects on postoperative neurocognitive function after surgical clipping of a UIA. However, this detrimental effect was small, and based on the group-rate analysis, the authors conclude that successful and meticulous surgical clipping of a UIA does not adversely affect postoperative cognitive function.

Postshunt Cognitive and Functional Improvement in Idiopathic Normal Pressure Hydrocephalus

Neurosurgery 68:416–419, 2011 DOI: 10.1227/NEU.0b013e3181ff9d01

Improvement in gait after shunt placement has been well documented in idiopathic normal pressure hydrocephalus (iNPH); however, controversy remains regarding the extent and pattern of postsurgical cognitive changes. Conflicting findings may be explained by variability in both test selection and follow-up intervals across studies. Furthermore, most investigations lack a control group, making it difficult to disentangle practice effects from a true treatment effect.

OBJECTIVE: To examine postshunt changes in a sample of well-characterized iNPH participants compared with a group of age- and education-matched healthy control subjects.

METHODS: We identified 12 participants with iNPH undergoing shunt placement and 9 control participants. All participants were evaluated with comprehensive neuropsychological testing and standardized gait assessment at baseline and were followed up for 6 months.

RESULTS: Repeated-measures analysis of variance revealed a significant group- (iNPH and control) by-time (baseline and 6 months) interaction for Trailmaking Test B: (P< .003) and Symbol Digit Modalities (P< .02), with greater improvement in iNPH participants relative to control subjects. In addition, the iNPH group showed greater improvement in gait (P< .001) and caregivers reported improved activities of daily living (P , .01) and reduced caregiver distress (P< .01).

CONCLUSION: This study demonstrates improvements in mental tracking speed and sustained attention 6 months after shunt placement in iNPH. The present investigation is the first study to use a controlled design to show that cognitive improvement in iNPH is independent of practice effects. Furthermore, these findings indicate functional and quality-of-life improvements for both the shunt responder and their caregiver.

Awake Surgery for Nonlanguage Mapping

Neurosurgery 66:523-529, 2010 DOI: 10.1227/01.NEU.0000364996.97762.73

During the past decade, numerous reports have supported the contribution  of awake mapping in surgical removal of brain lesions in eloquent areas, with a significant  increase of the extent of resection while minimizing the risk of permanent deficit—and  even improving quality of life.

METHODS: Most of these awake procedures were performed in patients with lesions in  language areas, to avoid postoperative aphasia. Surprisingly, mapping of nonlanguage  functions received less attention, despite the possible consequences of deficits other than  aphasia on daily life. Visuospatial and cognitive deficits are reported after brain surgery,  because of more objective and extensive neuropsychological assessments.

RESULTS AND CONCLUSION: This review provides new insights into the indications of  awake craniotomies for nonlanguage mapping in surgery for lesions in areas not related  to language processing.

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