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ResearchIn-Press PreviewNeuroscienceOncology Open Access | 10.1172/JCI168035

Postoperative risk of IDH mutant glioma-associated seizures and their potential management with IDH mutant inhibitors

Michael Drumm,1 Wenxia Wang,1 Thomas K. Sears,1 Kirsten Bell-Burdett,2 Rodrigo Javier,3 Kristen Y. Cotton,4 Brynna T. Webb,5 Kayla T. Byrne,6 Dusten Unruh,7 Vineeth Thirunavu,1 Jordain Walshon,1 Alicia Steffens,1 Kathleen McCortney,1 Rimas V. Lukas,8 Joanna J. Phillips,9 Esraa Mohamed,9 John D. Finan,10 Lucas Santana-Santos,11 Amy B. Heimberger,1 Colin K. Franz,12 Jonathan E. Kurz,13 Jessica W. Templer,8 Geoffrey T. Swanson,5 and Craig Horbinski1

1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Department of Preventive Medicine, Northwestern University, Chicago, United States of America

3Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, United States of America

4Department of Medicine, University of Illinois at Chicago, Chicago, United States of America

5Department of Pharmacology, Northwestern University, Chicago, United States of America

6Department of Medicine, Northwestern University, Chicago, United States of America

7Bio-Techne, Minneapolis, United States of America

8Ken & Ruth Davee Department of Neurology, Northwestern University, Chicago, United States of America

9Department of Neurological Surgery, Brain Tumor Center, UCSF, San Francisco, United States of America

10Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, United States of America

11Department of Pathology, Northwestern University, Chicago, United States of America

12Biologics Laboratory, Shirley Ryan AbilityLab, Chicago, United States of America

13Merck & Co, Inc, North Wales, United States of America

Find articles by Drumm, M. in: JCI | PubMed | Google Scholar

1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Department of Preventive Medicine, Northwestern University, Chicago, United States of America

3Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, United States of America

4Department of Medicine, University of Illinois at Chicago, Chicago, United States of America

5Department of Pharmacology, Northwestern University, Chicago, United States of America

6Department of Medicine, Northwestern University, Chicago, United States of America

7Bio-Techne, Minneapolis, United States of America

8Ken & Ruth Davee Department of Neurology, Northwestern University, Chicago, United States of America

9Department of Neurological Surgery, Brain Tumor Center, UCSF, San Francisco, United States of America

10Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, United States of America

11Department of Pathology, Northwestern University, Chicago, United States of America

12Biologics Laboratory, Shirley Ryan AbilityLab, Chicago, United States of America

13Merck & Co, Inc, North Wales, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Department of Preventive Medicine, Northwestern University, Chicago, United States of America

3Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, United States of America

4Department of Medicine, University of Illinois at Chicago, Chicago, United States of America

5Department of Pharmacology, Northwestern University, Chicago, United States of America

6Department of Medicine, Northwestern University, Chicago, United States of America

7Bio-Techne, Minneapolis, United States of America

8Ken & Ruth Davee Department of Neurology, Northwestern University, Chicago, United States of America

9Department of Neurological Surgery, Brain Tumor Center, UCSF, San Francisco, United States of America

10Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, United States of America

11Department of Pathology, Northwestern University, Chicago, United States of America

12Biologics Laboratory, Shirley Ryan AbilityLab, Chicago, United States of America

13Merck & Co, Inc, North Wales, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Department of Preventive Medicine, Northwestern University, Chicago, United States of America

3Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, United States of America

4Department of Medicine, University of Illinois at Chicago, Chicago, United States of America

5Department of Pharmacology, Northwestern University, Chicago, United States of America

6Department of Medicine, Northwestern University, Chicago, United States of America

7Bio-Techne, Minneapolis, United States of America

8Ken & Ruth Davee Department of Neurology, Northwestern University, Chicago, United States of America

9Department of Neurological Surgery, Brain Tumor Center, UCSF, San Francisco, United States of America

10Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, United States of America

11Department of Pathology, Northwestern University, Chicago, United States of America

12Biologics Laboratory, Shirley Ryan AbilityLab, Chicago, United States of America

13Merck & Co, Inc, North Wales, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Department of Preventive Medicine, Northwestern University, Chicago, United States of America

3Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, United States of America

4Department of Medicine, University of Illinois at Chicago, Chicago, United States of America

5Department of Pharmacology, Northwestern University, Chicago, United States of America

6Department of Medicine, Northwestern University, Chicago, United States of America

7Bio-Techne, Minneapolis, United States of America

8Ken & Ruth Davee Department of Neurology, Northwestern University, Chicago, United States of America

9Department of Neurological Surgery, Brain Tumor Center, UCSF, San Francisco, United States of America

10Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, United States of America

11Department of Pathology, Northwestern University, Chicago, United States of America

12Biologics Laboratory, Shirley Ryan AbilityLab, Chicago, United States of America

13Merck & Co, Inc, North Wales, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Department of Preventive Medicine, Northwestern University, Chicago, United States of America

3Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, United States of America

4Department of Medicine, University of Illinois at Chicago, Chicago, United States of America

5Department of Pharmacology, Northwestern University, Chicago, United States of America

6Department of Medicine, Northwestern University, Chicago, United States of America

7Bio-Techne, Minneapolis, United States of America

8Ken & Ruth Davee Department of Neurology, Northwestern University, Chicago, United States of America

9Department of Neurological Surgery, Brain Tumor Center, UCSF, San Francisco, United States of America

10Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, United States of America

11Department of Pathology, Northwestern University, Chicago, United States of America

12Biologics Laboratory, Shirley Ryan AbilityLab, Chicago, United States of America

13Merck & Co, Inc, North Wales, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Department of Preventive Medicine, Northwestern University, Chicago, United States of America

3Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, United States of America

4Department of Medicine, University of Illinois at Chicago, Chicago, United States of America

5Department of Pharmacology, Northwestern University, Chicago, United States of America

6Department of Medicine, Northwestern University, Chicago, United States of America

7Bio-Techne, Minneapolis, United States of America

8Ken & Ruth Davee Department of Neurology, Northwestern University, Chicago, United States of America

9Department of Neurological Surgery, Brain Tumor Center, UCSF, San Francisco, United States of America

10Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, United States of America

11Department of Pathology, Northwestern University, Chicago, United States of America

12Biologics Laboratory, Shirley Ryan AbilityLab, Chicago, United States of America

13Merck & Co, Inc, North Wales, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Department of Preventive Medicine, Northwestern University, Chicago, United States of America

3Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, United States of America

4Department of Medicine, University of Illinois at Chicago, Chicago, United States of America

5Department of Pharmacology, Northwestern University, Chicago, United States of America

6Department of Medicine, Northwestern University, Chicago, United States of America

7Bio-Techne, Minneapolis, United States of America

8Ken & Ruth Davee Department of Neurology, Northwestern University, Chicago, United States of America

9Department of Neurological Surgery, Brain Tumor Center, UCSF, San Francisco, United States of America

10Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, United States of America

11Department of Pathology, Northwestern University, Chicago, United States of America

12Biologics Laboratory, Shirley Ryan AbilityLab, Chicago, United States of America

13Merck & Co, Inc, North Wales, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Department of Preventive Medicine, Northwestern University, Chicago, United States of America

3Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, United States of America

4Department of Medicine, University of Illinois at Chicago, Chicago, United States of America

5Department of Pharmacology, Northwestern University, Chicago, United States of America

6Department of Medicine, Northwestern University, Chicago, United States of America

7Bio-Techne, Minneapolis, United States of America

8Ken & Ruth Davee Department of Neurology, Northwestern University, Chicago, United States of America

9Department of Neurological Surgery, Brain Tumor Center, UCSF, San Francisco, United States of America

10Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, United States of America

11Department of Pathology, Northwestern University, Chicago, United States of America

12Biologics Laboratory, Shirley Ryan AbilityLab, Chicago, United States of America

13Merck & Co, Inc, North Wales, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Department of Preventive Medicine, Northwestern University, Chicago, United States of America

3Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, United States of America

4Department of Medicine, University of Illinois at Chicago, Chicago, United States of America

5Department of Pharmacology, Northwestern University, Chicago, United States of America

6Department of Medicine, Northwestern University, Chicago, United States of America

7Bio-Techne, Minneapolis, United States of America

8Ken & Ruth Davee Department of Neurology, Northwestern University, Chicago, United States of America

9Department of Neurological Surgery, Brain Tumor Center, UCSF, San Francisco, United States of America

10Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, United States of America

11Department of Pathology, Northwestern University, Chicago, United States of America

12Biologics Laboratory, Shirley Ryan AbilityLab, Chicago, United States of America

13Merck & Co, Inc, North Wales, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Department of Preventive Medicine, Northwestern University, Chicago, United States of America

3Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, United States of America

4Department of Medicine, University of Illinois at Chicago, Chicago, United States of America

5Department of Pharmacology, Northwestern University, Chicago, United States of America

6Department of Medicine, Northwestern University, Chicago, United States of America

7Bio-Techne, Minneapolis, United States of America

8Ken & Ruth Davee Department of Neurology, Northwestern University, Chicago, United States of America

9Department of Neurological Surgery, Brain Tumor Center, UCSF, San Francisco, United States of America

10Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, United States of America

11Department of Pathology, Northwestern University, Chicago, United States of America

12Biologics Laboratory, Shirley Ryan AbilityLab, Chicago, United States of America

13Merck & Co, Inc, North Wales, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Department of Preventive Medicine, Northwestern University, Chicago, United States of America

3Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, United States of America

4Department of Medicine, University of Illinois at Chicago, Chicago, United States of America

5Department of Pharmacology, Northwestern University, Chicago, United States of America

6Department of Medicine, Northwestern University, Chicago, United States of America

7Bio-Techne, Minneapolis, United States of America

8Ken & Ruth Davee Department of Neurology, Northwestern University, Chicago, United States of America

9Department of Neurological Surgery, Brain Tumor Center, UCSF, San Francisco, United States of America

10Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, United States of America

11Department of Pathology, Northwestern University, Chicago, United States of America

12Biologics Laboratory, Shirley Ryan AbilityLab, Chicago, United States of America

13Merck & Co, Inc, North Wales, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Department of Preventive Medicine, Northwestern University, Chicago, United States of America

3Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, United States of America

4Department of Medicine, University of Illinois at Chicago, Chicago, United States of America

5Department of Pharmacology, Northwestern University, Chicago, United States of America

6Department of Medicine, Northwestern University, Chicago, United States of America

7Bio-Techne, Minneapolis, United States of America

8Ken & Ruth Davee Department of Neurology, Northwestern University, Chicago, United States of America

9Department of Neurological Surgery, Brain Tumor Center, UCSF, San Francisco, United States of America

10Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, United States of America

11Department of Pathology, Northwestern University, Chicago, United States of America

12Biologics Laboratory, Shirley Ryan AbilityLab, Chicago, United States of America

13Merck & Co, Inc, North Wales, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Department of Preventive Medicine, Northwestern University, Chicago, United States of America

3Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, United States of America

4Department of Medicine, University of Illinois at Chicago, Chicago, United States of America

5Department of Pharmacology, Northwestern University, Chicago, United States of America

6Department of Medicine, Northwestern University, Chicago, United States of America

7Bio-Techne, Minneapolis, United States of America

8Ken & Ruth Davee Department of Neurology, Northwestern University, Chicago, United States of America

9Department of Neurological Surgery, Brain Tumor Center, UCSF, San Francisco, United States of America

10Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, United States of America

11Department of Pathology, Northwestern University, Chicago, United States of America

12Biologics Laboratory, Shirley Ryan AbilityLab, Chicago, United States of America

13Merck & Co, Inc, North Wales, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Department of Preventive Medicine, Northwestern University, Chicago, United States of America

3Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, United States of America

4Department of Medicine, University of Illinois at Chicago, Chicago, United States of America

5Department of Pharmacology, Northwestern University, Chicago, United States of America

6Department of Medicine, Northwestern University, Chicago, United States of America

7Bio-Techne, Minneapolis, United States of America

8Ken & Ruth Davee Department of Neurology, Northwestern University, Chicago, United States of America

9Department of Neurological Surgery, Brain Tumor Center, UCSF, San Francisco, United States of America

10Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, United States of America

11Department of Pathology, Northwestern University, Chicago, United States of America

12Biologics Laboratory, Shirley Ryan AbilityLab, Chicago, United States of America

13Merck & Co, Inc, North Wales, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Department of Preventive Medicine, Northwestern University, Chicago, United States of America

3Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, United States of America

4Department of Medicine, University of Illinois at Chicago, Chicago, United States of America

5Department of Pharmacology, Northwestern University, Chicago, United States of America

6Department of Medicine, Northwestern University, Chicago, United States of America

7Bio-Techne, Minneapolis, United States of America

8Ken & Ruth Davee Department of Neurology, Northwestern University, Chicago, United States of America

9Department of Neurological Surgery, Brain Tumor Center, UCSF, San Francisco, United States of America

10Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, United States of America

11Department of Pathology, Northwestern University, Chicago, United States of America

12Biologics Laboratory, Shirley Ryan AbilityLab, Chicago, United States of America

13Merck & Co, Inc, North Wales, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Department of Preventive Medicine, Northwestern University, Chicago, United States of America

3Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, United States of America

4Department of Medicine, University of Illinois at Chicago, Chicago, United States of America

5Department of Pharmacology, Northwestern University, Chicago, United States of America

6Department of Medicine, Northwestern University, Chicago, United States of America

7Bio-Techne, Minneapolis, United States of America

8Ken & Ruth Davee Department of Neurology, Northwestern University, Chicago, United States of America

9Department of Neurological Surgery, Brain Tumor Center, UCSF, San Francisco, United States of America

10Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, United States of America

11Department of Pathology, Northwestern University, Chicago, United States of America

12Biologics Laboratory, Shirley Ryan AbilityLab, Chicago, United States of America

13Merck & Co, Inc, North Wales, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Department of Preventive Medicine, Northwestern University, Chicago, United States of America

3Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, United States of America

4Department of Medicine, University of Illinois at Chicago, Chicago, United States of America

5Department of Pharmacology, Northwestern University, Chicago, United States of America

6Department of Medicine, Northwestern University, Chicago, United States of America

7Bio-Techne, Minneapolis, United States of America

8Ken & Ruth Davee Department of Neurology, Northwestern University, Chicago, United States of America

9Department of Neurological Surgery, Brain Tumor Center, UCSF, San Francisco, United States of America

10Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, United States of America

11Department of Pathology, Northwestern University, Chicago, United States of America

12Biologics Laboratory, Shirley Ryan AbilityLab, Chicago, United States of America

13Merck & Co, Inc, North Wales, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Department of Preventive Medicine, Northwestern University, Chicago, United States of America

3Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, United States of America

4Department of Medicine, University of Illinois at Chicago, Chicago, United States of America

5Department of Pharmacology, Northwestern University, Chicago, United States of America

6Department of Medicine, Northwestern University, Chicago, United States of America

7Bio-Techne, Minneapolis, United States of America

8Ken & Ruth Davee Department of Neurology, Northwestern University, Chicago, United States of America

9Department of Neurological Surgery, Brain Tumor Center, UCSF, San Francisco, United States of America

10Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, United States of America

11Department of Pathology, Northwestern University, Chicago, United States of America

12Biologics Laboratory, Shirley Ryan AbilityLab, Chicago, United States of America

13Merck & Co, Inc, North Wales, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Department of Preventive Medicine, Northwestern University, Chicago, United States of America

3Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, United States of America

4Department of Medicine, University of Illinois at Chicago, Chicago, United States of America

5Department of Pharmacology, Northwestern University, Chicago, United States of America

6Department of Medicine, Northwestern University, Chicago, United States of America

7Bio-Techne, Minneapolis, United States of America

8Ken & Ruth Davee Department of Neurology, Northwestern University, Chicago, United States of America

9Department of Neurological Surgery, Brain Tumor Center, UCSF, San Francisco, United States of America

10Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, United States of America

11Department of Pathology, Northwestern University, Chicago, United States of America

12Biologics Laboratory, Shirley Ryan AbilityLab, Chicago, United States of America

13Merck & Co, Inc, North Wales, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Department of Preventive Medicine, Northwestern University, Chicago, United States of America

3Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, United States of America

4Department of Medicine, University of Illinois at Chicago, Chicago, United States of America

5Department of Pharmacology, Northwestern University, Chicago, United States of America

6Department of Medicine, Northwestern University, Chicago, United States of America

7Bio-Techne, Minneapolis, United States of America

8Ken & Ruth Davee Department of Neurology, Northwestern University, Chicago, United States of America

9Department of Neurological Surgery, Brain Tumor Center, UCSF, San Francisco, United States of America

10Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, United States of America

11Department of Pathology, Northwestern University, Chicago, United States of America

12Biologics Laboratory, Shirley Ryan AbilityLab, Chicago, United States of America

13Merck & Co, Inc, North Wales, United States of America

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1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Department of Preventive Medicine, Northwestern University, Chicago, United States of America

3Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, United States of America

4Department of Medicine, University of Illinois at Chicago, Chicago, United States of America

5Department of Pharmacology, Northwestern University, Chicago, United States of America

6Department of Medicine, Northwestern University, Chicago, United States of America

7Bio-Techne, Minneapolis, United States of America

8Ken & Ruth Davee Department of Neurology, Northwestern University, Chicago, United States of America

9Department of Neurological Surgery, Brain Tumor Center, UCSF, San Francisco, United States of America

10Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, United States of America

11Department of Pathology, Northwestern University, Chicago, United States of America

12Biologics Laboratory, Shirley Ryan AbilityLab, Chicago, United States of America

13Merck & Co, Inc, North Wales, United States of America

Find articles by Templer, J. in: JCI | PubMed | Google Scholar |

1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Department of Preventive Medicine, Northwestern University, Chicago, United States of America

3Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, United States of America

4Department of Medicine, University of Illinois at Chicago, Chicago, United States of America

5Department of Pharmacology, Northwestern University, Chicago, United States of America

6Department of Medicine, Northwestern University, Chicago, United States of America

7Bio-Techne, Minneapolis, United States of America

8Ken & Ruth Davee Department of Neurology, Northwestern University, Chicago, United States of America

9Department of Neurological Surgery, Brain Tumor Center, UCSF, San Francisco, United States of America

10Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, United States of America

11Department of Pathology, Northwestern University, Chicago, United States of America

12Biologics Laboratory, Shirley Ryan AbilityLab, Chicago, United States of America

13Merck & Co, Inc, North Wales, United States of America

Find articles by Swanson, G. in: JCI | PubMed | Google Scholar

1Department of Neurological Surgery, Northwestern University, Chicago, United States of America

2Department of Preventive Medicine, Northwestern University, Chicago, United States of America

3Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, United States of America

4Department of Medicine, University of Illinois at Chicago, Chicago, United States of America

5Department of Pharmacology, Northwestern University, Chicago, United States of America

6Department of Medicine, Northwestern University, Chicago, United States of America

7Bio-Techne, Minneapolis, United States of America

8Ken & Ruth Davee Department of Neurology, Northwestern University, Chicago, United States of America

9Department of Neurological Surgery, Brain Tumor Center, UCSF, San Francisco, United States of America

10Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, United States of America

11Department of Pathology, Northwestern University, Chicago, United States of America

12Biologics Laboratory, Shirley Ryan AbilityLab, Chicago, United States of America

13Merck & Co, Inc, North Wales, United States of America

Find articles by Horbinski, C. in: JCI | PubMed | Google Scholar |

Published April 27, 2023 - More info

J Clin Invest. https://doi.org/10.1172/JCI168035.
Copyright © 2023, Drumm et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published April 27, 2023 - Version history
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Abstract

Seizures are a frequent complication of adult-type diffuse gliomas, and are often difficult to control with medications. Gliomas with mutations in isocitrate dehydrogenase 1 or 2 (IDHmut) are more likely than IDH wild-type (IDHwt) gliomas to cause seizures as part of their initial clinical presentation. However, whether IDHmut is also associated with seizures during the remaining disease course, and whether IDHmut inhibitors can reduce seizure risk, are unclear. Clinical multivariable analyses showed that preoperative seizures, glioma location, extent of resection, and glioma molecular subtype (including IDHmut status) all contribute to postoperative seizure risk in adult-type diffuse glioma patients, and that postoperative seizures are often associated with tumor recurrence. Experimentally, the metabolic product of IDHmut, D-2-hydroxyglutarate, rapidly synchronizes neuronal spike firing in a seizure-like manner, but only when nonneoplastic glial cells are present. In vitro and in vivo models can recapitulate IDHmut glioma-associated seizures, and IDHmut inhibitors currently being evaluated in glioma clinical trials inhibit seizures in those models, independent of their effects on glioma growth. These data show that postoperative seizure risk in adult-type diffuse gliomas varies in large part by molecular subtype, and that IDHmut inhibitors could play a key role in mitigating such risk in IDHmut glioma patients.

Graphical Abstract
graphical abstract
Supplemental material

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View Supplemental Video 1: Time lapse imaging of IDHmut glioma infiltrating spheroid. GFP-labeled patient-derived TB09 glioma line was co-cultured with spheroid, and imaging was taken over a span of 6 hours.

View Supplemental Video 2: EEG recording of IDHmut glioma-engrafted mouse during generalized seizure. Blue trace = EEG channel 1, orange trace = EEG channel 2, green trace = EMG lead.

View Supplemental Video 3: Recording of IDHmut glioma-engrafted mouse during generalized seizure.

Version history
  • Version 1 (April 27, 2023): In-Press Preview
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