Altered amygdala volumes and microstructure in focal epilepsy patients with tonic-clonic seizures, ictal, and post-convulsive central apnea

Claudia Zeicu; Antoine Legouhy; Catherine A Scott; Joana F A Oliveira; Gavin P Winston; John S Duncan; Sjoerd B Vos; Maria Thom; Samden Lhatoo; Hui Zhang; Ronald M Harper; Beate Diehl

doi:10.1111/epi.17804

Altered amygdala volumes and microstructure in focal epilepsy patients with tonic-clonic seizures, ictal, and post-convulsive central apnea

Epilepsia. 2023 Dec;64(12):3307-3318. doi: 10.1111/epi.17804. Epub 2023 Oct 31.

Authors

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

3}, Joana F A Oliveira^{1

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

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 the volume and microstructure of the amygdala, a key structure that can trigger apnea in people with focal epilepsy, stratified by the presence or absence of FBTCS, ictal central apnea (ICA), and post-convulsive central apnea (PCCA).

Methods: Seventy-three patients with focal impaired awareness seizures without FBTC seizures (FBTCneg group) and 30 with FBTCS (FBTCpos group) recorded during video electroencephalography (VEEG) with respiratory monitoring were recruited prospectively during presurgical investigations. We acquired high-resolution T1-weighted anatomic and multi-shell diffusion images, and computed neurite orientation dispersion and density imaging (NODDI) metrics in all patients with epilepsy and 69 healthy controls. Amygdala volumetric and microstructure alterations were compared between three groups: healthy subjects, FBTCneg and FBTCpos groups. The FBTCpos group was further subdivided by the presence of ICA and PCCA, verified by VEEG.

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

Significance: Individuals with FBTCpos and PCCA 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.

MeSH terms

Amygdala / diagnostic imaging
Apnea
Electroencephalography / methods
Epilepsies, Partial* / complications
Epilepsies, Partial* / diagnostic imaging
Epilepsy*
Epilepsy, Tonic-Clonic*
Humans
Seizures
Sleep Apnea, Central* / diagnostic imaging
Sleep Apnea, Central* / etiology

Abstract

MeSH terms

Grants and funding