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[Preprint]. 2023 Mar 17:2023.03.16.23287369.

doi: 10.1101/2023.03.16.23287369.

Altered Amygdala Volumes and Microstructure in Focal Epilepsy Patients with Tonic-Clonic Seizures, Ictal and Post-Ictal Central Apnea

Claudia Zeicu¹, Antoine Legouhy², Catherine A Scott^{1

3}, Joana F A Oliveira^{1

3}, Gavin Winston^{1

4

5}, John S Duncan¹, Sjoerd B Vos^{2

6

7}, Maria Thom¹, Samden Lhatoo⁸, Hui Zhang², Ronald M Harper^{9

10}, Beate Diehl^{1

3}

Affiliations

¹ Department of Clinical and Experimental Epilepsy, Queen Square Institute of Neurology, University College London, London, United Kingdom.
² Centre for Medical Image Computing and Department of Computer Science, University College London, London, United Kingdom.
³ Department of Clinical Neurophysiology, University College London Hospitals NHS Foundation Trust National Hospital for Neurology and Neurosurgery, London, United Kingdom.
⁴ Epilepsy Society MRI Unit, Chalfont St Peter, United Kingdom.
⁵ Division of Neurology, Department of Medicine, Queen's University, Kingston, Ontario, Canada.
⁶ Neuroradiological Academic Unit, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom.
⁷ Centre for Microscopy, Characterisation, and Analysis, The University of Western Australia, Nedlands, Australia.
⁸ Department of Neurology, University of Texas Health Sciences Center at Houston, Houston, Texas, USA.
⁹ Brain Research Institute, University of California at Los Angeles, California, USA.
¹⁰ Department of Neurobiology, David Geffen School of Medicine, University of California at Los Angeles, California, USA.

PMID: 36993530
PMCID: PMC10055587
DOI: 10.1101/2023.03.16.23287369

Altered Amygdala Volumes and Microstructure in Focal Epilepsy Patients with Tonic-Clonic Seizures, Ictal and Post-Ictal Central Apnea

Claudia Zeicu et al. medRxiv. 2023.

[Preprint]. 2023 Mar 17:2023.03.16.23287369.

doi: 10.1101/2023.03.16.23287369.

Authors

Affiliations

¹ Department of Clinical and Experimental Epilepsy, Queen Square Institute of Neurology, University College London, London, United Kingdom.
² Centre for Medical Image Computing and Department of Computer Science, University College London, London, United Kingdom.
³ Department of Clinical Neurophysiology, University College London Hospitals NHS Foundation Trust National Hospital for Neurology and Neurosurgery, London, United Kingdom.
⁴ Epilepsy Society MRI Unit, Chalfont St Peter, United Kingdom.
⁵ Division of Neurology, Department of Medicine, Queen's University, Kingston, Ontario, Canada.
⁶ Neuroradiological Academic Unit, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom.
⁷ Centre for Microscopy, Characterisation, and Analysis, The University of Western Australia, Nedlands, Australia.
⁸ Department of Neurology, University of Texas Health Sciences Center at Houston, Houston, Texas, USA.
⁹ Brain Research Institute, University of California at Los Angeles, California, USA.
¹⁰ Department of Neurobiology, David Geffen School of Medicine, University of California at Los Angeles, California, USA.

PMID: 36993530
PMCID: PMC10055587
DOI: 10.1101/2023.03.16.23287369

Update in

Altered amygdala volumes and microstructure in focal epilepsy patients with tonic-clonic seizures, ictal, and post-convulsive central apnea.
Zeicu C, Legouhy A, Scott CA, Oliveira JFA, Winston GP, Duncan JS, Vos SB, Thom M, Lhatoo S, Zhang H, Harper RM, Diehl B. Zeicu C, et al. Epilepsia. 2023 Dec;64(12):3307-3318. doi: 10.1111/epi.17804. Epub 2023 Oct 31. Epilepsia. 2023. PMID: 37857465 Free PMC article.

Abstract

Objectives: Sudden unexpected death in epilepsy (SUDEP) is a leading cause of death for patients with epilepsy; however, the pathophysiology remains unclear. Focal-to-bilateral tonic-clonic seizures (FBTCS) are a major risk factor, and centrally-mediated respiratory depression may increase the risk further. Here, we determined volume and microstructure of the amygdala, a key structure that can trigger apnea in people with focal epilepsy, stratified by presence or absence of FBTCS, ictal central apnea (ICA) and post-ictal central apnea (PICA).

Methods: 73 patients with only-focal seizures and 30 with FBTCS recorded during video EEG (VEEG) with respiratory monitoring were recruited prospectively during presurgical investigations. We acquired high-resolution T1-weighted anatomical and multi-shell diffusion images, and computed neurite orientation dispersion and density imaging (NODDI) metrics in all epilepsy patients and 69 healthy controls. Amygdala volumetric and microstructure alterations were compared between healthy subjects, and patients with only-focal seizures or FBTCS The FBTCS group was further subdivided by presence of ICA and PICA, verified by VEEG.

Results: Bilateral amygdala volumes were significantly increased in the FBTCS cohort compared to healthy controls and the focal cohort. Patients with recorded PICA had the highest increase in bilateral amygdala volume of the FBTCS cohort.Amygdala neurite density index (NDI) values were significantly decreased in both the focal and FBTCS groups relative to healthy controls, with values in the FBTCS group being the lowest of the two. The presence of PICA was associated with significantly lower NDI values vs the non-apnea FBTCS group (p=0.004).

Significance: Individuals with FBTCS and PICA show significantly increased amygdala volumes and disrupted architecture bilaterally, with greater changes on the left side. The structural alterations reflected by NODDI and volume differences may be associated with inappropriate cardiorespiratory patterns mediated by the amygdala, particularly after FBTCS. Determination of amygdala volumetric and architectural changes may assist identification of individuals at risk.

Keywords: NODDI; SUDEP; amygdala; apnea; diffusion MRI; tonic-clonic seizures.

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Conflict of interest statement

Disclosure of Conflicts of Interest None of the authors has any conflict of interest to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Figures

**Figure 1.**
Amygdala Volume Tukey Box Plots. Abbreviations: FBTCS, focal-to-bilateral tonic-clonic seizure; ICA, ictal central apnea; PICA, post-ictal central apnea. (*<0.05, **<0.01, ***<0.001) **(A)** left amygdala volume mm³ in 172 participants subdivided into healthy controls, focal-unaware seizure cohort and FBTCS. **(B)** right amygdala volume mm³ in 172 participants subdivided into healthy controls, focal-unaware seizure cohort and FBTCS. **(C)** left amygdala volume groups further divided in conjunction with the presence or absence of ICA. **(D)** right amygdala volume groups further divided in conjunction with the presence or absence of ICA. **(E)** left amygdala volume groups further divided in conjunction with the presence or absence of PICA. **(F)** left amygdala volume groups further divided in conjunction with the presence or absence of PICA.

**Figure 2.**
NDI Tukey Box Plots. Abbreviations: NDI, neurite dispersion index; FBTCS, focal to bilateral tonic-clonic seizure; ICA, ictal central apnea; PICA, post-ictal central apnea. (*<0.05, **<0.01, ***<0.001). **(A)** left amygdala NDI in 172 participants subdivided into healthy controls, focal-unaware seizure cohort and FBTCS. **(B)** right amygdala NDI in 172 participants subdivided into healthy controls, focal-unaware seizure cohort and FBTCS. **(C)** left amygdala NDI groups further divided in conjunction with the presence or absence of ICA. **(D)** right amygdala NDI groups further divided in conjunction with the presence or absence of ICA. **(E)** left amygdala NDI groups further divided in conjunction with the presence or absence of PICA. **(F)** left amygdala volume groups further divided in conjunction with the presence or absence of PICA.

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References

1. Surges R, Thijs RD, Tan HL, Sander JW. Sudden unexpected death in epilepsy: risk factors and potential pathomechanisms. Nat Rev Neurol. 2009. Sep 11;5(9):492–504. - PubMed
1. Ryvlin P, Nashef L, Lhatoo SD, Bateman LM, Bird J, Bleasel A, et al. Incidence and mechanisms of cardiorespiratory arrests in epilepsy monitoring units (MORTEMUS): a retrospective study. Lancet Neurol. 2013. Oct; 12(10):966–77. - PubMed
1. Vilella L, Lacuey N, Hampson JP, Rani MRS, Loparo K, Sainju RK, et al. Incidence, Recurrence, and Risk Factors for Peri-ictal Central Apnea and Sudden Unexpected Death in Epilepsy. Front Neurol. 2019. Mar 1;10. - PMC - PubMed
1. Vilella L, Lacuey N, Hampson JP, Rani MRS, Sainju RK, Friedman D, et al. Postconvulsive central apnea as a biomarker for sudden unexpected death in epilepsy (SUDEP). Neurology. 2019. Jan 15;92(3):e171–82. - PMC - PubMed
1. Allen LA, Vos SB, Kumar R, Ogren JA, Harper RK, Winston GP, et al. Cerebellar, limbic, and midbrain volume alterations in sudden unexpected death in epilepsy. Epilepsia. 2019. Apr 14;60(4):718–29. - PMC - PubMed

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This is a preprint.

Altered Amygdala Volumes and Microstructure in Focal Epilepsy Patients with Tonic-Clonic Seizures, Ictal and Post-Ictal Central Apnea

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Altered Amygdala Volumes and Microstructure in Focal Epilepsy Patients with Tonic-Clonic Seizures, Ictal and Post-Ictal Central Apnea

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