Most patients with non lesional temporal lobe epilepsy (NL TLE) will have th e findings of hippocampal sclerosis (HS) on a high resolution MRI. However, a si gnificant minority of patients with NLTLE and electroclinically well lateral i zed temporal lobe seizures have no evidence of HS on MRI. Many of these patients have concordant hypometabolism on fluorodeoxyglucose PET([ 18F]FDG PET). Th e pathophysiological basis of this latter group remains uncertain. We aimed to det ermine whether NLTLE without HS on MRI represents a variant of or a different cl inicopathological syndrome from that of NLTLE with HS on MRI. The clinical, EEG, [18F]FDG PET, histopathological and surgical outcomes of 30 consecutive NLTL E patients with well lateralized EEG but without HS on MRI (HS ve TLE) were comp ared with 30 consecutive age and sexmatched NLTLE patients with well lateraliz ed EEG with HS on MRI (HS+ve TLE). Both the HS+ve TLE group and the HS ve TLE patients had a high degree of [18F] FDG PET concordant lateralization (26 o ut of 30 HS ve TLE versus 27 out of 27 HS+ve TLE). HS ve TLE patients had more widespread hypometabolism on [18F]FDG PET by blinded visual analysis [odds r ati o (OR = +∞(2.51-+∞), P = 0.001]. The HS ve TLE group less frequently had a history of febrile convulsions [OR = 0.077 (0.002-0.512), P = 0.002], more c om monly had a delta rhythm at ictal onset [OR = 3.67 (0.97-20.47), P = 0.057], an d less frequently had histopathological evidence of HS [OR = 0 (0-0.85), P -0 . 031]. There was no significant difference in surgical outcome despite half of t h ose without HS having a hippocampal sparing procedure. Based on the findings ou tlined, HS ve PET positive TLE may be a surgically remediable syndrome distinc t from HS+ve TLE, with a pathophysiological basis that primarily involves later al temporal neocortical rather than mesial temporal structures. Most patients with non-lesional temporal lobe epilepsy (NL TLE) will have th e findings of hippocampal sclerosis (HS) on a high resolution MRI. However, a si gnificant minority of patients with NLTLE and electroclinically well lateral i zed temporal lobe seizures have no evidence of HS on MRI. Many of these patients have concordant hypometabolism on fluorodeoxyglucose PET ([18F] FDG PET). Th e pathophysiological basis of the latter group remains uncertain. We aimed to det ermine whether NLTLE without HS on MRI represents a variant of or a different cl inicopathological syndrome from that of NLTLE with HS on MRI. The clinical, EEG, [18F] FDG PET, histopathological and surgical outcomes of 30 consecutive NLTL E patients with well lateralized EEG but without HS on MRI (HS ve TLE) Both the HS + ve TLE group and the HS ve TLE patients had a high degree of [18F] FDG PET (HS + ve TLE) co ncordant lateralization (26 o ut of 30 HS ve TLE versus 27 out of 27 HS + ve TLE). HS ve TLE patients had more widespread hypometabolism on [18F] FDG PET by blinded visual analysis [odds r ati o (OR = + ∞ (2.51- + ∞), P = 0.001]. The HS ve TLE group less frequently had a history of febrile convulsions [OR = 0.077 (0.002-0.512), P = 0.002], more c om monly had a delta rhythm at ictal onset [OR = 3.67 (0.97-20.47), P = 0.057], an d less frequently had histopathological evidence of HS [OR = 0 (0-0.85), P -0.031]. There was no significant difference in the surgical outcome Despite half of th ose without HS having a hippocampal sparing procedure. Based on the findings ou tlined, HS ve PET positive TLE may be a surgically remediable syndrome distinc from HS + ve TLE, with a pathophysiological basis that incorporatedfts later al temporal neocortical rather than mesial temporal structures.