Distinct Patterns of Brain Metabolism in Patients at Risk of Sudden Unexpected Death in Epilepsy

Benjamin P Whatley; Joel S Winston; Luke A Allen; Sjoerd B Vos; Ashwani Jha; Catherine A Scott; April-Louise Smith; Fahmida A Chowdhury; Jamshed B Bomanji; Samden D Lhatoo; Ronald M Harper; Beate Diehl

doi:10.3389/fneur.2021.623358

Distinct Patterns of Brain Metabolism in Patients at Risk of Sudden Unexpected Death in Epilepsy

Front Neurol. 2021 Nov 24:12:623358. doi: 10.3389/fneur.2021.623358. eCollection 2021.

Authors

Benjamin P Whatley^{1

2}, Joel S Winston^{3

4

5

6}, Luke A Allen^{1

7

8}, Sjoerd B Vos^{7

8

9

10}, Ashwani Jha¹¹, Catherine A Scott^{1

8}, April-Louise Smith¹², Fahmida A Chowdhury¹, Jamshed B Bomanji¹², Samden D Lhatoo^{8

13

14}, Ronald M Harper^{8

15

16}, Beate Diehl^{1

7

8}

Affiliations

¹ Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, United Kingdom.
² Division of Neurology, Dalhousie University, Halifax, NS, Canada.
³ Department of Clinical Neurophysiology, National Hospital for Neurology and Neurosurgery, London, United Kingdom.
⁴ Wellcome Trust Centre for Human Neuroimaging, UCL Queen Square Institute of Neurology, London, United Kingdom.
⁵ Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
⁶ Department of Clinical Neurophysiology, King's College Hospital, London, United Kingdom.
⁷ Epilepsy Society MRI Unit, Chalfont St Peter, United Kingdom.
⁸ The Center for SUDEP Research, National Institutes of Neurological Disorders and Stroke, Bethesda, MD, United States.
⁹ Neuroradiological Academic Unit, Queen Square Institute of Neurology, University College London, London, United Kingdom.
¹⁰ Centre for Medical Image Computing, University College London, London, United Kingdom.
¹¹ Department of Brain Repair and Rehabilitation, UCL Queen Square Institute of Neurology, London, United Kingdom.
¹² Institute of Nuclear Medicine, University College London, London, United Kingdom.
¹³ Epilepsy Center, Neurological Institute, University Hospitals Case Medical Center, Cleveland, OH, United States.
¹⁴ Department of Neurology, University of Texas Health Sciences Center at Houston, Houston, TX, United States.
¹⁵ Brain Research Institute, University of California, Los Angeles, Los Angeles, CA, United States.
¹⁶ Department of Neurobiology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, United States.

Abstract

Objective: To characterize regional brain metabolic differences in patients at high risk of sudden unexpected death in epilepsy (SUDEP), using fluorine-18-fluorodeoxyglucose positron emission tomography (¹⁸FDG-PET). Methods: We studied patients with refractory focal epilepsy at high (n = 56) and low (n = 69) risk of SUDEP who underwent interictal ¹⁸FDG-PET as part of their pre-surgical evaluation. Binary SUDEP risk was ascertained by thresholding frequency of focal to bilateral tonic-clonic seizures (FBTCS). A whole brain analysis was employed to explore regional differences in interictal metabolic patterns. We contrasted these findings with regional brain metabolism more directly related to frequency of FBTCS. Results: Regions associated with cardiorespiratory and somatomotor regulation differed in interictal metabolism. In patients at relatively high risk of SUDEP, fluorodeoxyglucose (FDG) uptake was increased in the basal ganglia, ventral diencephalon, midbrain, pons, and deep cerebellar nuclei; uptake was decreased in the left planum temporale. These patterns were distinct from the effect of FBTCS frequency, where increasing frequency was associated with decreased uptake in bilateral medial superior frontal gyri, extending into the left dorsal anterior cingulate cortex. Significance: Regions critical to cardiorespiratory and somatomotor regulation and to recovery from vital challenges show altered interictal metabolic activity in patients with frequent FBTCS considered to be at relatively high-risk of SUDEP, and shed light on the processes that may predispose patients to SUDEP.

Keywords: SUDEP; bilateral tonic-clonic seizure; cardiorespiratory regulation; central autonomic regulation; epilepsy; positron emission tomography.