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Focal Cooling for Drug-Resistant EpilepsyA Review

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Importance  Epilepsy affects at least 1.2% of the population, with one-third of cases considered to be drug-resistant epilepsy (DRE). For these cases, focal cooling therapy may be a potential avenue for treatment, offering hope to people with DRE for freedom from seizure. The therapy leverages neuroscience and engineering principles to deliver a reversible treatment unhindered by pharmacology.

Observations  Analogous to (but safer than) the use of global cooling in postcardiac arrest and neonatal ischemic injury, extensive research supports the premise that focal cooling as a long-term treatment for epilepsy could be effective. The potential advantages of focal cooling are trifold: stopping epileptiform discharges, seizures, and status epilepticus safely across species (including humans).

Conclusions and Relevance  This Review presents the most current evidence supporting focal cooling in epilepsy. Cooling has been demonstrated as a potentially safe and effective treatment modality for DRE, although it is not yet ready for use in humans outside of randomized clinical trials. The Review will also offer a brief overview of the technical challenges related to focal cooling in humans, including the optimal device design and cooling parameters.

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Article Information

Accepted for Publication: May 20, 2022.

Published Online: July 25, 2022. doi:10.1001/jamaneurol.2022.1936

Corresponding Author: Daniel M. Goldenholz, MD, PhD, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Baker 5, Boston, MA 02215 (daniel.goldenholz@bidmc.harvard.edu).

Author Contributions: Drs Goldenholz and Niesvizky-Kogan had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Niesvizky-Kogan, D. Goldenholz.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Niesvizky-Kogan, Bass.

Critical revision of the manuscript for important intellectual content: Niesvizky-Kogan, S. Goldenholz, D. Goldenholz.

Obtained funding: D. Goldenholz.

Administrative, technical, or material support: Niesvizky-Kogan, Bass, D. Goldenholz.

Supervision: D. Goldenholz.

Conflict of Interest Disclosures: None reported.

Funding/Support: This study was funded in part by the National Institutes of Health (grant KL2 5KL2TR002542).

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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