Compared with patients with grade II or III left temporal lobe glioma, patients with grade IV tumors exhibit greater difficulty with verbal learning, processing speed, executive functioning, and language. Differences in NCF associated with glioma grade were independent of lesion volume, seizure status, and antiepileptic or steroid use, lending support to the concept of "lesion momentum" as a primary contributor to deficits in NCF of newly diagnosed patients prior to surgery.
Background Fatigue is a consistently reported, severe symptom among patients with gliomas throughout the disease trajectory. Genomic pathways associated with fatigue in glioma patients have yet to be identified. Methods Clinical factors (performance status, tumor details, age, gender) were collected by chart review on glioma patients with fatigue (“I have lack of energy” on Functional Assessment of Cancer Therapy-Brain), as well as available genotyping data. Candidate genes in clock and inflammatory pathways were identified from a literature review, of which 50 single nucleotide polymorphisms (SNPs) in 7 genes were available. Clinical factors and SNPs identified by univariate analyses were included in a multivariate model for moderate-severe fatigue. Results The study included 176 patients (median age = 47 years, 67% males). Moderate-severe fatigue was reported by 43%. Results from multivariate analysis revealed poor performance status and 2 SNPs were associated with fatigue severity. Moderate-severe fatigue was more common in patients with poor performance status (OR = 3.52, P < .01). For each additional copy of the minor allele in rs934945 (PER2) the odds of fatigue decreased (OR = 0.51, P < .05). For each additional copy of the minor allele in rs922270 (ARTNL2) the odds of fatigue increased (OR = 2.38, P < .01). Both of these genes are important in the circadian clock pathway, which has been implicated in diurnal preference, and duration and quality of sleep. No genes in the inflammatory pathway were associated with fatigue in the current study. Conclusions Identifying patients at highest risk for fatigue during treatment allows for improved clinical monitoring and enrichment of patient selection for clinical trials.
Objective Impaired neurocognitive function (NCF) is a well‐established consequence of pediatric medulloblastoma (MB) and its treatments. However, the frequency and features of neurocognitive dysfunction in adult‐onset MB patients are largely unknown. Methods Adult patients (≥ 18 years) with MB who had received formal neurocognitive evaluation (N = 27) were identified. Demographic, medical, and treatment histories were extracted from the medical record. Lesion properties on MRI were analyzed and used to evaluate lesion‐symptom mapping further. Demographically adjusted z‐scores were calculated for each neurocognitive test and used to assess impairment frequency. Regression analyses were conducted to identify clinical and paraclinical factors associated with impaired NCF. Results Mean age of the patient sample was 33 years (SD = 11) at the time of MB diagnosis. Prior therapy included surgical resection (89%), radiation (70%), and chemotherapy (26%). A significant proportion of patients were impaired on tests of verbal learning and memory (32%), executive function (29%), and naming (18%). Age, education, lesion size, time from surgery, and number of chemotherapy cycles had the greatest contribution to test performance in random‐forest regression models. Conclusion This study identifies frequent impairment of NCF in adult patients with MB, particularly in the domains of learning and memory and executive function. Neurocognitive impairment is influenced by patients' demographic, disease, and treatment history. Further study is warranted to characterize the clinical impact of adult MB more fully.
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