427be a stress biomarker in TLE in that it correlates inversely with memory scores and
hippocampal volume. In addition, the symmetric extratemporal atrophic patterns
may be related to damage of neuronal networks and epileptogenesis in TLE.
High-magnetic-fi eld MRI and long-term video EEG in a rat model of febrile
status epilepticus (FSE) has revealed that reduced amygdala T2 relaxation times can
predict TLE (Choy et al. 2014 ). Reduced T2 values likely represent paramagnetic
susceptibility effects derived from increased unsaturated venous hemoglobin,
suggesting augmented oxygen utilization after FSE termination. Use of
deoxyhemoglobin- sensitive MRI sequences enabled visualization of the predictive
changes on lower-fi eld, clinically relevant scanners. This novel MRI signature rep-
resents a predictive biomarker for early identifi cation of FSE individuals who are
likely to develop TLE and are candidates for preventive therapy.
Quantitative measurements by MRI of overall brain volume (gray matter, white
matter, and CSF) in temporal lobe epilepsy are clinically meaningful biomarkers that
are associated with increased cognitive morbidity. Focal cortical dysplasia (FCD) is
a common cause of pharmacoresistant epilepsy that is amenable to treatment by
surgical resection. The identifi cation of structural FCD by MRI can contribute to the
detection of the epileptogenic zone and improve the outcome of epilepsy surgery.
New magnetic resonance-based techniques, such as MR spectroscopy, fMRI, and
fMRI/EEG, are more frequently being used to increase the yield of MRI in detecting
abnormalities associated with epilepsy.
Noninvasive imaging of brain infl ammation would be helpful in determining its role
in epileptogenesis and serve as a biomarker for epilepsy. The current imaging toolbox
is limited by the range of neuroinfl ammatory targets that can be visualized directly.
Research in this area will further advance as highly specifi c ligands and reproducible
as well as practical imaging approaches become available (Amhaoul et al. 2014 ).
Molecular and functional interactions between high mobility group box-1
(HMGB1) and the N-methyl-d-aspartate receptor (NMDAR), two proteins playing
a key role in neuronal hyperexcitability, have been studied in primary cultures of
mouse hippocampal neurons (Balosso et al. 2014 ). HMGB1 normally resides in the
nucleus to regulate transcription, but translocates to the cytoplasm in response to
cellular injury and is released into the extracellular milieu where it functions as a
pro-infl ammatory cytokine biomarker. Disulfi de HMGB1 increased phosphoryla-
tion of the NR2B subunit of the NMDAR, which is known to increase Ca 2+ channel
permeability and increase NMDA-induced neuronal cell death in vitro and enhance
kainate-induced seizures in vivo. This novel molecular neuronal pathway activated
by HMGB1 could be targeted in vivo to prevent neurodegeneration and seizures
mediated by excessive NMDARs stimulation.
Genetics/Genomics of Epilepsy
Considerable information is being generated by advances in genomic technologies.
Integration of these techniques with functional biology and bioinformatics will
improve our understanding of the genetic contribution to epilepsy, use of genetic
Personalized Management of Epilepsy