Association of piriform cortex resection with surgical outcomes in patients with temporal lobe epilepsy

Matthias J. Koepp, Marian Galovic, Irene Baudracco, Evan Wright-Goff, Galo Pillajo, Parashkev Nachev, Britta Wandschneider, Friedrich Woermann, Pamela Thompson, Sallie Baxendale, Andrew W. McEvoy, Mark Nowell, Matteo Mancini, Sjoerd B. Vos, Gavin P. Winston, Rachel Sparks, Ferran Prados, Anna Miserocchi, Jane De Tisi, Louis André Van GraanRoman Rodionov, Chengyuan Wu, Mahdi Alizadeh, Lauren Kozlowski, Ashwini D. Sharan, Lohith G. Kini, Kathryn A. Davis, Brian Litt, Sebastien Ourselin, Solomon L. Moshé, Josemir W.A. Sander, Wolfgang Löscher, John S. Duncan

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Importance: A functional area associated with the piriform cortex, termed area tempestas, has been implicated in animal studies as having a crucial role in modulating seizures, but similar evidence is limited in humans. Objective: To assess whether removal of the piriform cortex is associated with postoperative seizure freedom in patients with temporal lobe epilepsy (TLE) as a proof-of-concept for the relevance of this area in human TLE. Design, Setting, and Participants: This cohort study used voxel-based morphometry and volumetry to assess differences in structural magnetic resonance imaging (MRI) scans in consecutive patients with TLE who underwent epilepsy surgery in a single center from January 1, 2005, through December 31, 2013. Participants underwent presurgical and postsurgical structural MRI and had at least 2 years of postoperative follow-up (median, 5 years; range, 2-11 years). Patients with MRI of insufficient quality were excluded. Findings were validated in 2 independent cohorts from tertiary epilepsy surgery centers. Study follow-up was completed on September 23, 2016, and data were analyzed from September 24, 2016, through April 24, 2018. Exposures: Standard anterior temporal lobe resection. Main Outcomes and Measures: Long-Term postoperative seizure freedom. Results: In total, 107 patients with unilateral TLE (left-sided in 68; 63.6% women; median age, 37 years [interquartile range {IQR}, 30-45 years]) were included in the derivation cohort. Reduced postsurgical gray matter volumes were found in the ipsilateral piriform cortex in the postoperative seizure-free group (n = 46) compared with the non-seizure-free group (n = 61). A larger proportion of the piriform cortex was resected in the seizure-free compared with the non-seizure-free groups (median, 83% [IQR, 64%-91%] vs 52% [IQR, 32%-70%]; P <.001). The results were seen in left-and right-sided TLE and after adjusting for clinical variables, presurgical gray matter alterations, presurgical hippocampal volumes, and the proportion of white matter tract disconnection. Findings were externally validated in 2 independent cohorts (31 patients; left-sided TLE in 14; 54.8% women; median age, 41 years [IQR, 31-46 years]). The resected proportion of the piriform cortex was individually associated with seizure outcome after surgery (derivation cohort area under the curve, 0.80 [P <.001]; external validation cohorts area under the curve, 0.89 [P <.001]). Removal of at least half of the piriform cortex increased the odds of becoming seizure free by a factor of 16 (95% CI, 5-47; P <.001). Other mesiotemporal structures (ie, hippocampus, amygdala, and entorhinal cortex) and the overall resection volume were not associated with outcomes. Conclusions and Relevance: These results support the importance of resecting the piriform cortex in neurosurgical treatment of TLE and suggest that this area has a key role in seizure generation..

Original languageEnglish (US)
Pages (from-to)690-700
Number of pages11
JournalJAMA Neurology
Issue number6
StatePublished - Jun 2019

ASJC Scopus subject areas

  • Clinical Neurology


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