title: Towards prognostic biomarkers from BOLD fluctuations to differentiate a first epileptic seizure from new-onset epilepsy.
abstract: The diagnosis of epilepsy cannot be reliably made prior to a patient's second seizure in most cases. Therefore, adequate diagnostic tools are needed to differentiate subjects with a first seizure from those with a seizure preceding the onset of epilepsy. The objective was to explore spontaneous blood oxygen level-dependent (BOLD) fluctuations in subjects with a first-ever seizure and patients with new-onset epilepsy (NOE), and to find characteristic biomarkers for seizure recurrence after the first seizure.
  
  
  
  We examined 17 first-seizure subjects, 19 patients with new-onset epilepsy (NOE), and 18 healthy controls. All subjects underwent clinical investigation and received electroencephalography and resting-state functional magnetic resonance imaging (MRI). The BOLD time series were analyzed in terms of regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuations (fALFFs).
  
  
  
  We found significantly stronger amplitudes (higher fALFFs) in patients with NOE relative to first-seizure subjects and healthy controls. The frequency range of 73-198 mHz (slow-3 subband) appeared most useful for discriminating patients with NOE from first-seizure subjects. The ReHo measure did not show any significant differences.
  
  
  
  The fALFF appears to be a noninvasive measure that characterizes spontaneous BOLD fluctuations and shows stronger amplitudes in the slow-3 subband of patients with NOE relative first-seizure subjects and healthy controls. A larger study population with follow-up is required to determine whether fALFF holds promise as a potential biomarker for identifying subjects at increased risk to develop epilepsy.
authors.affiliation: Departments of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Lalit
authors.initials: L
authors.lastname: Gupta
authors.affiliation: Department of Neurology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Rick
authors.initials: R
authors.lastname: Janssens
authors.affiliation: Department of Neurology, Maastricht University Medical Center, Maastricht, The Netherlands.|Academic Center for Epileptology Kempenhaeghe/Maastricht University Medical Center, Heeze and Maastricht, The Netherlands.
authors.forename: Mariëlle C G
authors.initials: MC
authors.lastname: Vlooswijk
authors.affiliation: Department of Neurology, Maastricht University Medical Center, Maastricht, The Netherlands.|Academic Center for Epileptology Kempenhaeghe/Maastricht University Medical Center, Heeze and Maastricht, The Netherlands.|School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.
authors.forename: Rob P W
authors.initials: RP
authors.lastname: Rouhl
authors.affiliation: Academic Center for Epileptology Kempenhaeghe/Maastricht University Medical Center, Heeze and Maastricht, The Netherlands.|Epilepsy Center Kempenhaeghe, Heeze, The Netherlands.
authors.forename: Anton
authors.initials: A
authors.lastname: de Louw
authors.affiliation: Department of Neurology, Maastricht University Medical Center, Maastricht, The Netherlands.|Academic Center for Epileptology Kempenhaeghe/Maastricht University Medical Center, Heeze and Maastricht, The Netherlands.|School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.|Epilepsy Center Kempenhaeghe, Heeze, The Netherlands.|Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors.forename: Albert P
authors.initials: AP
authors.lastname: Aldenkamp
authors.affiliation: Philips India Ltd., Bangalore, Karnataka, India.
authors.forename: Shrutin
authors.initials: S
authors.lastname: Ulman
authors.affiliation: Departments of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.|Epilepsy Center Kempenhaeghe, Heeze, The Netherlands.|Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors.forename: René M H
authors.initials: RM
authors.lastname: Besseling
authors.affiliation: Departments of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.|Academic Center for Epileptology Kempenhaeghe/Maastricht University Medical Center, Heeze and Maastricht, The Netherlands.|School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.
authors.forename: Paul A M
authors.initials: PA
authors.lastname: Hofman
authors.affiliation: Department of Clinical Neurophysiology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Vivianne H
authors.initials: VH
authors.lastname: van Kranen-Mastenbroek
authors.affiliation: Department of Clinical Neurophysiology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Danny M
authors.initials: DM
authors.lastname: Hilkman
authors.affiliation: Departments of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.|School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.
authors.forename: Jacobus F A
authors.initials: JF
authors.lastname: Jansen
authors.affiliation: Departments of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.|School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.
authors.forename: Walter H
authors.initials: WH
authors.lastname: Backes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D004562:Electrocardiography; D004569:Electroencephalography; D004827:Epilepsy / Q000097:blood* / Q000000981:diagnostic imaging* / Q000209:etiology / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: BOLD time series; First-seizure; Functional magnetic resonance imaging; Low frequency oscillations; New-onset epilepsy; Regional homogeneity