A Novel, Noninvasive, Predictive Epilepsy Biomarker with Clinical Potential

被引:67
作者
Choy, ManKin [1 ,2 ]
Dube, Celine M. [2 ]
Patterson, Katelin [2 ]
Barnes, Samuel R. [5 ]
Maras, Pamela [2 ]
Blood, Arlin B. [6 ]
Hasso, Anton N. [3 ]
Obenaus, Andre [6 ]
Baram, Tallie Z. [1 ,2 ,4 ]
机构
[1] Univ Calif Irvine, Dept Pediat, Irvine, CA 92697 USA
[2] Univ Calif Irvine, Dept Pediat & Anat Neurobiol, Irvine, CA 92697 USA
[3] Univ Calif Irvine, Dept Radiol Sci, Irvine, CA 92697 USA
[4] Univ Calif Irvine, Dept Neurol, Irvine, CA 92697 USA
[5] Loma Linda Univ, Sch Med, Dept Radiat Med, Loma Linda, CA 92350 USA
[6] Loma Linda Univ, Sch Med, Dept Pediat, Loma Linda, CA 92350 USA
关键词
biomarker; epilepsy; febrile seizures; inflammation; MRI; predictive; TEMPORAL-LOBE EPILEPSY; EXPERIMENTAL FEBRILE SEIZURES; CEREBRAL BLOOD-FLOW; STATUS EPILEPTICUS; DEVELOPING BRAIN; KAINIC ACID; LONG-TERM; ELECTRICAL STIMULATION; UNPROVOKED SEIZURES; HIPPOCAMPAL INJURY;
D O I
10.1523/JNEUROSCI.4806-13.2014
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 T-2 relaxation times in high-magnetic-field MRI hours after FSE predicted experimental TLE. Reduced T-2 values likely represented paramagnetic susceptibility effects derived from increased unsaturated venous hemoglobin, suggesting augmented oxygen utilization after FSE termination. Indeed, T-2 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.
引用
收藏
页码:8672 / 8684
页数:13
相关论文
共 86 条
[1]   Prevalence of epilepsy in rural Kansas [J].
Ablah, Elizabeth ;
Hesdorffer, Dale C. ;
Liu, Yi ;
Paschal, Angelia M. ;
Hawley, Suzanne ;
Thurman, David ;
Hauser, W. Allen .
EPILEPSY RESEARCH, 2014, 108 (04) :792-801
[2]   FACTORS PROGNOSTIC OF UNPROVOKED SEIZURES AFTER FEBRILE CONVULSIONS [J].
ANNEGERS, JF ;
HAUSER, WA ;
SHIRTS, SB ;
KURLAND, LT .
NEW ENGLAND JOURNAL OF MEDICINE, 1987, 316 (09) :493-498
[3]   Stressed-out, or in (utero)? [J].
Avishai-Eliner, S ;
Brunson, KL ;
Sandman, CA ;
Baram, TZ .
TRENDS IN NEUROSCIENCES, 2002, 25 (10) :518-524
[4]   Does Acquired Epileptogenesis in the Immature Brain Require Neuronal Death? [J].
Baram, Tallie Z. ;
Jensen, Frances E. ;
Brooks-Kayal, Amy .
EPILEPSY CURRENTS, 2011, 11 (01) :21-26
[5]   Febrile seizures: An appropriate-aged model suitable for long-term studies [J].
Baram, TZ ;
Gerth, A ;
Schultz, L .
DEVELOPMENTAL BRAIN RESEARCH, 1997, 98 (02) :265-270
[6]   Synchronized network activity in developing rat hippocampus involves regional hyperpolarization-activated cyclic nucleotide-gated (HCN) channel function [J].
Bender, RA ;
Galindo, R ;
Mameli, M ;
Gonzalez-Vega, R ;
Valenzuela, CF ;
Baram, TZ .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2005, 22 (10) :2669-2674
[7]   Mossy fiber plasticity and enhanced hippocampal excitability, without hippocampal cell loss or altered neurogenesis, in an animal model of prolonged febrile seizures [J].
Bender, RA ;
Dubé, C ;
Gonzalez-Vega, R ;
Mina, EW ;
Baram, TZ .
HIPPOCAMPUS, 2003, 13 (03) :399-412
[8]   Mapping thalamocortical network pathology in temporal lobe epilepsy [J].
Bernhardt, Boris C. ;
Bernasconi, Neda ;
Kim, Hosung ;
Bernasconi, Andrea .
NEUROLOGY, 2012, 78 (02) :129-136
[9]   Positive and negative network correlations in temporal lobe epilepsy [J].
Blumenfeld, H ;
McNally, KA ;
Vanderhill, SD ;
Paige, AL ;
Chung, R ;
Davis, K ;
Norden, AD ;
Stokking, R ;
Studholme, C ;
Novotny, EJ ;
Zubal, IG ;
Spencer, SS .
CEREBRAL CORTEX, 2004, 14 (08) :892-902
[10]   Magnetic resonance imaging follow-up of progressive hippocampal changes in a mouse model of mesial temporal lobe epilepsy [J].
Bouilleret, V ;
Nehlig, A ;
Marescaux, C ;
Namer, IJ .
EPILEPSIA, 2000, 41 (06) :642-650