68 This abnormality is thought to primarily reflect, neuronal loss,69 but its fluctuation over time observed in

patients scanned twice also suggest underlying functional disturbances of the GABA)A receptor complex.70,71 FMZ-PET has also been extensively evaluated in patients with GSK2656157 drug-resistant partial epilepsy, and has consistently demonstrated more focal abnormalities than FDG-PET.72 However, the issue as to whether FMZ-PET allows a more precise delineation of the epileptogenic zone than FDG-PET remains a matter of debate.55,73 In particular, in patients with a normal MRI, FMZ-PET might suffer a higher rate of negative or falsely localizing findings than FDG-PET.55,70,71,74 Finally, in Inhibitors,research,lifescience,medical patients with TLE and MRI signs of hippocampal sclerosis, FMZ-PET might, disclose periventricular white matter increased binding of [11C]Flumazenil, thought to reflect microscopic heterotopia, which were found associated Inhibitors,research,lifescience,medical with poor postoperative seizure outcome.75 This finding, if replicated, could support, the clinical utility

of FMZ-PET as a prognostic tool in TLE patients contemplating Inhibitors,research,lifescience,medical surgery. In patient with tuberous sclerosis and multiple tubers, PET using [11C]alpha-methyl-L-tryptophan (AMT) appears to be the only interictal imaging investigation that can specifically identify which of the multiple tubers is responsible for the seizure disorder, by showing an increased AMT

uptake within that tuber.76 However, this pattern is only observed in half of the patients.77-79 More recently, several studies have used different, markers of 5-HT1A receptors in patients with drug-resistant TLE, including [11C]WAY100635, [18F]FC-WAY, Inhibitors,research,lifescience,medical and [18F]MPPF, and consistently showed major decreased of binding potential within the epileptogenic temporal lobe.80-83 Whether these PET investigations will prove Inhibitors,research,lifescience,medical more clinically useful than, or complementary to, FDG and FMZ-PET remain to be elucidated. Ictal SPECT Ictal SPECT remains the only imaging method that can routinely capture clinically overt seizures, regardless of the patient, ictal movements. The most typical pattern observed on ictal SPECT images is a focal area of hyperpcrfusion, thought to reflect the ictal discharge, with surrounding hypoperfusion. The delineation of these abnormalities is optimized by subtracting these interictal from ictal SPECT images from the same patient, and coregistering the resulting data on his or her MRI (subtraction ictal SPECT coregistered with MRI, SISCOM).84 Recent attempts to detect significant, ictal hyperperfusion by comparing ictal SPECT to a database of interictal SPECT performed in normal subjects also proved promising.85 The earlier the timing of injection after seizure onset, the more sensitive and reliable the results of ictal SPECT.