title: A novel, noninvasive, predictive epilepsy biomarker with clinical potential.
abstract: A significant proportion of temporal lobe epilepsy (TLE), a common, intractable brain disorder, arises in children with febrile status epilepticus (FSE). Preventative therapy development is hampered by our inability to identify early the FSE individuals who will develop TLE. In a naturalistic rat model of FSE, we used high-magnetic-field MRI and long-term video EEG to seek clinically relevant noninvasive markers of epileptogenesis and found that reduced amygdala T2 relaxation times in high-magnetic-field MRI hours after FSE predicted experimental TLE. Reduced T2 values likely represented paramagnetic susceptibility effects derived from increased unsaturated venous hemoglobin, suggesting augmented oxygen utilization after FSE termination. Indeed, T2 correlated with energy-demanding intracellular translocation of the injury-sensor high-mobility group box 1 (HMGB1), a trigger of inflammatory cascades implicated in epileptogenesis. Use of deoxyhemoglobin-sensitive MRI sequences enabled visualization of the predictive changes on lower-field, clinically relevant scanners. This novel MRI signature delineates the onset and suggests mechanisms of epileptogenesis that follow experimental FSE.
authors: Department of Pediatrics, Department of Anatomy/Neurobiology.
authors: ManKin
authors: M
authors: Choy
authors: Department of Anatomy/Neurobiology.
authors: Celine M
authors: CM
authors: Dubé
authors: Department of Anatomy/Neurobiology.
authors: Katelin
authors: K
authors: Patterson
authors: Department of Radiation Medicine and.
authors: Samuel R
authors: http://orcid.org/0000-0002-1065-8442
authors: SR
authors: Barnes
authors: Department of Anatomy/Neurobiology.
authors: Pamela
authors: P
authors: Maras
authors: Department of Pediatrics, Loma Linda University School of Medicine, Loma Linda, California 92350.
authors: Arlin B
authors: AB
authors: Blood
authors: Department of Radiological Sciences, and.
authors: Anton N
authors: AN
authors: Hasso
authors: Department of Pediatrics, Loma Linda University School of Medicine, Loma Linda, California 92350.
authors: Andre
authors: A
authors: Obenaus
authors: Department of Pediatrics, Department of Anatomy/Neurobiology, Department of Neurology, University of California-Irvine, Irvine, California 92697, and tallie@uci.edu.
authors: Tallie Z
authors: TZ
authors: Baram
mesh_terms: D000818:Animals; D015415:Biomarkers; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000379:methods*; D004827:Epilepsy / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D003294:Seizures, Febrile / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D013226:Status Epilepticus / Q000150:complications* / Q000473:pathology / Q000503:physiopathology
chemical_list: D015415:Biomarkers
keywords: MRI; biomarker; epilepsy; febrile seizures; inflammation; predictive