Randomized Controlled Trial

. 2025 Apr;172(2):417-428.

doi: 10.1007/s11060-024-04931-9. Epub 2025 Jan 23.

Improving postsurgical paresis in brain tumor patients by transcranial magnetic stimulation

Tizian Rosenstock^#^{1

2}, Thomas Picht^#^{1

3}, Melina Engelhardt^#^{1

4}, Ulrike Grittner^#⁵, Maximilian Mönch^#⁵, Peter Vajkoczy^#¹, José Pedro Lavrador^#⁶, Ana Mirallave-Pescador^#⁷, Francesco Vergani^#⁶, Maximilian Schwendner^#^{8

9}, Axel Schroeder^#⁸, Leonie Kram^#^{8

9}, Haosu Zhang^#^{8

9}, Sujit Prabhu^#¹⁰, Sarah Prinsloo^#¹⁰, Bernhard Meyer^#⁸, Sebastian Ille^#^{8

9}, Sandro M Krieg^#^{11

12}

Affiliations

¹ Department of Neurosurgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.
² BIH Charité Digital Clinician Scientist Program, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, BIH Biomedical Innovation Academy, Charitéplatz 1, 10117, Berlin, Germany.
³ Cluster of Excellence: "Matters of Activity. Image Space Material, " Humboldt University, Unter den Linden 6, 10099, Berlin, Germany.
⁴ Einstein Center for Neurosciences, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.
⁵ Institute of Biometry and Clinical Epidemiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.
⁶ Neurosurgical Department, King's College Hospital Foundation Trust, London, UK.
⁷ Neurophysiology Department, King's College Hospital Foundation Trust, London, UK.
⁸ Department of Neurosurgery, School of Medicine, Technical University of Munich, Klinikum rechts der Isar, Munich, Germany.
⁹ Department of Neurosurgery, Heidelberg University Hospital, Ruprecht-Karls-University, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.
¹⁰ Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
¹¹ Department of Neurosurgery, School of Medicine, Technical University of Munich, Klinikum rechts der Isar, Munich, Germany. Sandro.Krieg@med.uni-heidelberg.de.
¹² Department of Neurosurgery, Heidelberg University Hospital, Ruprecht-Karls-University, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany. Sandro.Krieg@med.uni-heidelberg.de.

^# Contributed equally.

PMID: 39847143
PMCID: PMC11937064
DOI: 10.1007/s11060-024-04931-9

Randomized Controlled Trial

Improving postsurgical paresis in brain tumor patients by transcranial magnetic stimulation

Tizian Rosenstock et al. J Neurooncol. 2025 Apr.

. 2025 Apr;172(2):417-428.

doi: 10.1007/s11060-024-04931-9. Epub 2025 Jan 23.

Authors

Affiliations

¹ Department of Neurosurgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.
² BIH Charité Digital Clinician Scientist Program, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, BIH Biomedical Innovation Academy, Charitéplatz 1, 10117, Berlin, Germany.
³ Cluster of Excellence: "Matters of Activity. Image Space Material, " Humboldt University, Unter den Linden 6, 10099, Berlin, Germany.
⁴ Einstein Center for Neurosciences, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.
⁵ Institute of Biometry and Clinical Epidemiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.
⁶ Neurosurgical Department, King's College Hospital Foundation Trust, London, UK.
⁷ Neurophysiology Department, King's College Hospital Foundation Trust, London, UK.
⁸ Department of Neurosurgery, School of Medicine, Technical University of Munich, Klinikum rechts der Isar, Munich, Germany.
⁹ Department of Neurosurgery, Heidelberg University Hospital, Ruprecht-Karls-University, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.
¹⁰ Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
¹¹ Department of Neurosurgery, School of Medicine, Technical University of Munich, Klinikum rechts der Isar, Munich, Germany. Sandro.Krieg@med.uni-heidelberg.de.
¹² Department of Neurosurgery, Heidelberg University Hospital, Ruprecht-Karls-University, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany. Sandro.Krieg@med.uni-heidelberg.de.

^# Contributed equally.

PMID: 39847143
PMCID: PMC11937064
DOI: 10.1007/s11060-024-04931-9

Abstract

Background and objectives: Recently, reduction of transcallosal inhibition by contralateral navigated repetitive transcranial magnetic stimulation (nrTMS) improved neurorehabilitation of glioma patients with new postoperative paresis. This multicentric study examines the effect of postoperative nrTMS in brain tumor patients to treat surgery-related upper extremity paresis.

Methods: This is a secondary analysis of two randomized and three one-arm studies in brain tumor patients with new/progressive postoperative paresis. Patients underwent either low frequency contralesional nrTMS or sham stimulation followed by physiotherapy. Outcome was assessed on postoperative day 1, 7, and after 3 months using British Medical Research Council score (BMRC), Fugl-Meyer assessment (FMA), Karnofsky Performance Scale (KPS) and National Institutes of Health Stroke Scale (NIHSS).

Results: A total of 135 patients (mean age of 53.8 years, 60 women) were included, of whom 51 patients were treated in RCTs (30 treatment group, 21 sham group) and 84 in prospective, single-arm studies. Linear mixed models showed an advantage for the treatment group for the BMRC (7 days: OR 3.28; 95%CI: 1.08-9.99; 3 months: OR 2.03, 95%CI: 0.65-6.39) and KPS (7 days: mean difference (MD) 11, 95%CI: 2-19; 3 months: MD 11, 95%CI: 2-20), less pronounced for the FMA (7 days: MD 0.28, 95%CI: -0.34-0.9; 3 months: MD 0.14, 95%CI: -0.52-0.81). A stronger treatment effect was evident with proven ischemia on the postoperative MRI. To observe an improvement by at least one grade at 3 months, the number needed to treat (NNT) for the entire cohort is 4 (BMRC) and 3 patients (KPS), respectively.

Conclusion: Our multicenter data confirm the positive treatment effect of nrTMS to reduce transcallosal inhibition with a considerably low NNT - especially if caused by ischemia.

Keywords: Glioma; Navigated transcranial magnetic stimulation (nTMS); Paresis.

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Conflict of interest statement

Declarations. Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organization for the submitted work.BM received honoraria, consulting fees, and research grants from Medtronic (Meerbusch, Germany), Icotec AG (Altstätten, Switzerland), and Relievant Medsystems Inc. (Sunnyvale, CA, USA); honoraria, and research grants from Ulrich Medical (Ulm, Germany); honoraria and consulting fees from Spineart Deutschland GmbH (Frankfurt, Germany) and DePuy Synthes (West Chester, PA, USA); and royalties from Spineart Deutschland GmbH (Frankfurt, Germany). SK is a consultant for Ulrich Medical (Ulm, Germany) and Need Inc. (Santa Monica, CA, USA). TP, SK, SI and BM are consultants for Brainlab AG (Munich, Germany).SI, TP, and SK received honoraria from Nexstim Plc (Helsinki, Finland) for a webinar. TP received research grants from Carl Zeiss Meditec (Oberkochen, Germany) and Olympus Corporation (Center Valley, PA, USA).However, all authors declare that they have no conflict of interest regarding the materials used or the results presented in this study. All authors declare no other relationships or activities that could appear to have influenced the submitted work. Ethical approval: We performed the study in accordance with the Declaration of Helsinki. There were 4 centers involved in this study: Charité – Universitätsmedizin Berlin (I), Technical University of Munich (II), King’s College Hospital, London (III), MD Anderson Cancer Center (IV). The study was conducted as an RCT at 2 sites (I; II), with the study transitioning to a single-arm study at one site after recruitment completion (II). All included patients provided written informed consent at each center. Local ethics boards reviewed and approved the study protocol (registration numbers: Munich NCT03982329 and 12/15, Berlin EA4/132/15, London: 20230701NCR; Houston: NCT03606161). Clinical trial registration/local institutional approval: Munich: NCT03982329, Local institutional registration: 12/15; Berlin: Deutsches Register für klinische Studien (DRKS00010043), Ethics Committee of the Charité (EA4/132/15); London: Local institutional registration 20230701NCR; Houston: NCT03606161.

Figures

**Fig. 1**
Scatter plot showing the outcome parameters by time point and group. All recorded values (without imputations) are shown for each time point, separated by groups (purple = Sham, blue = rTMS) for the BMRC (a, POD1: rTMS n = 90, sham n = 21; POD7: rTMS n = 96, sham n = 21; POM3: rTMS n = 71, sham n = 15), FMA (b, POD1: rTMS n = 73, sham n = 19; POD7: rTMS n = 75, sham n = 19; POM3: rTMS n = 29, sham n = 10), KPS (c, POD1: rTMS n = 96, sham n = 21; POD7: rTMS n = 106, sham n = 21; POM3: rTMS n = 78, sham n = 15) and the NIHSS (d, POD1: rTMS n = 85, sham n = 21; POD7: rTMS n = 83, sham n = 21; POM3: rTMS n = 57, sham n = 15). Colored dots represent values for individual subjects. Colored lines correspond to estimated group averages using locally estimated scatterplot smoothing (Loess) with the respective 95% confidence intervals

**Fig. 2**
Forest plots based on imputed data showing the respective treatment effects. Treatment effects for the entire study population and for subgroups (patients with ischemia, patients with preserved postoperative MEPs) are shown. Estimates are based on multiple imputed datasets (30 complete datasets). a: Analysis of the BMRC based on ordinal logistic mixed models (random intercept models, random intercepts for patients) adjusted for the BMRC values before intervention, presence of SMA tumor, tumor histology and tumor location, time point, interaction of time point and treatment allocation, center and interaction of center and treatment allocation (OR: odds ratio). b: Analysis of the FMA based on mixed models (random intercept models, random intercepts for patients) with log-transformed FMA values, adjusted for log-transformed FMA values before intervention, presence of SMA tumor, tumor histology and tumor location, time point, interaction of time point and treatment allocation, center and interaction of center and treatment allocation. c: Analysis of NIHSS based on mixed models (random intercept models, random intercepts for patients) adjusted for NIHSS values before intervention, presence of SMA tumor, tumor histology and tumor location, time point, interaction of time point and treatment allocation, center and interaction of center and treatment allocation. d: Analysis of the KPS based on mixed models (random intercept models, random intercepts for patients) adjusted for KPS values before intervention, presence of SMA tumor, tumor histology and tumor location, time point, interaction of time point and treatment allocation, center and interaction of center and treatment allocation

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Improving postsurgical paresis in brain tumor patients by transcranial magnetic stimulation

Affiliations

Improving postsurgical paresis in brain tumor patients by transcranial magnetic stimulation

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Medical