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

Abstract

To the Editor: We read with great interest this letter1 about our paper2 on the impact of WHO tumour grading on the motor cortex excitability of diffuse gliomas measured by navigated transcranial magnetic stimulation (nTMS). We recognize the interest about new applications of nTMS beyond a simple localization tool towards a functional characterization of eloquent areas in tumour surgery. Also, we share the authors’ vision of bringing more advanced motor functional mapping—such as short interval intracortical inhibition—to the neuro-oncology field.3 Combined together, anatomical and functional information are likely to improve the existing preoperative stratification risk models to further support patients’ counselling before surgery.4,5 The authors1 raised two main points for discussion. The first one is related to a potential bias effect caused by the tumour characteristics (such as location) and the preoperative motor function, in the results supporting a more resilience of the upper limb motor function. We performed further analysis to clarify this issue. Taking the frontal lobe location as our base outcome—the frontal lobe location is predominant in this cohort (62.2% of patients)—the resting motor threshold (RMT) and the interhemispheric RMT ratio (iRMTr) for the upper and lower limbs and the WHO grading system is not significantly different (Figure). Therefore, the tumour anatomical characteristics did not seem to influence the excitability results identified in this cohort.FIGURE.: RMT and interhemispheric RMT Ratio of both upper and lower limbs per anatomical location.The second point concerning the preoperative assessment and postoperative motor outcome. A total of 7 patients had preoperative motor deficits, all with hemiparesis of similar MRC grades in the upper and lower limbs—in 5 patients 4/5 and in 2 patients 3/5, no improvement on preoperative steroids. These patients had involvement of the M1-CST complex (documented with nTMS and/or tractography) and not expected to recover with surgical resection. A total of 6 patients had new transitory postoperative motor deficits: 2 patients in the upper limb (3/5)—lesions embedded in the hand knob (WHO Grade 2 and Grade 4)—and 4 patients with hemiparesis predominant in the lower limb—1 patient had 3/5 and 3 patients had 4/5, all of them with lesions in the supplementary motor area (SMA) proper; 1 patient had WHO Grade 2 and 3 patients had WHO Grade 4 tumours. Apart from the fact that all the patients with a preoperative motor deficit had an abnormal cortical excitability score (CES > 0), no other significant differences were found in terms of RMT and iRMTr between patients with and without preoperative motor deficit. These results further emphasize the concept already mentioned in the letter1 that the motor deficit is a delayed presentation in the process of dysfunction of the M1-CST complex and that abnormal excitability can be identified even in patient with normal motor function. In terms of new postoperative deficits, we believe that the location within the hand knob and the SMA proper were determinant for the differences observed as no other nTMS related variables were significantly different. However, we do recognize the number of events were small and therefore the study is underpowered to answer this question. We share the commitment in further develop the preoperative mapping in order to improve the amount of information we can provide the patients, with particular relevance to the onco-functional balance on an individual basis. nTMS may even change the surgical approach or the surgical indication in selected cases.6 We support a shared decision-making process where patient's views, nTMS preoperative mapping, intraoperative neuromonitoring, and histological information are crucial in getting the best outcome in glioma surgery, particularly for challenging tumours centred in the motor cortex.7 Funding This study did not receive any funding or financial support. Disclosures The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.