With great interest we read the article by Wefel et al entitled “Neurocognitive function varies by IDH1 genetic mutation status in patients with malignant glioma prior to surgical resection,”1 recently published in Neuro-Oncology. We would like to congratulate the authors on their work, as neurocognitive function (NCF) is crucial for our patients’ quality of life and is gaining more attention in patient care. Nevertheless, there seem to be some shortcomings in interpreting the data.
Firstly, it is well known that most patients show neurocognitive decline upon diagnosis of both high- and low-grade gliomas.2,3 It has recently been pointed out that inflammatory reactions, patterns of DNA repair, and metabolism pathways are strongly associated with NCF.4 In the present study, the authors carried out an analysis separated by mutational status of isocitrate dehydrogenase (IDH) and evaluated the presence of preoperative NCF impairments in correlation with IDH mutation.
Although total lesion volume on fluid attenuated inversion recovery (FLAIR) (including peritumoral edema) was comparable in both groups, the patients’ age (P < .0001), Karnofsky Performance Index (P < .0001), and tumor volume on T1-MRI (without contrast) (P < .006) were significantly different. These differences are not corrected for statistically, which greatly limits the strengths of the conclusion. It may well be that the mean age difference of 17 years between the groups affects NCF as a result of reduced neuroplasticity with age.5,6 The given T1 and FLAIR volumes demonstrated significantly more edema compared with the actual tumor volume for IDH wild-type tumors. We agree that the IDH wild-type tumors may cause a larger, more aggressive infiltration of surrounding brain tissue. Nevertheless, the conclusion that genetic alterations of tumors alter NCF cannot be directly concluded.
Causal research on the origin of NCF impairments is cumbersome and has not yet yielded clear results. Most likely NCF impairment is due to infiltrative behavior of the tumors into subcortical networks,7 as this has been demonstrated in diffuse infiltrating low-grade gliomas.
With these limitations of current research, the cause of NCF impairments remains largely unclear. The effect of IDH mutational status on NCF is therefore still a matter of debate, as confounding factors like age may play an important role.
We congratulate the authors for their commitment to this crucial topic in the care of patients with gliomas.
References
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