Temporal lobe epilepsy is the commonest form of refractory focal epilepsy in adults. About 30% of temporal lobe epilepsy is due to foreign tissue lesions, whilst 60–70% is designated "non lesional" (NLTLE). The most common pathological substrate in this "non-lesional" group is hippocampal sclerosis (HS), present in a majority of medically refractory cases. Whilst it is difficult to give exact proportions, given that only patients with intractable seizures undergo full characterisation, around 70% of these patients with NLTLE are thought to have HS [1
]. It is estimated that at least 30% of patients with NLTLE have neither a foreign tissue temporal lobe lesion nor MRI evidence of HS (HS-ve).
A previous study by our group demonstrated significant clinicopathological and qualitative structural and functional imaging differences between TLE associated with hippocampal sclerosis (HS+ve) and TLE with no evidence of hippocampal sclerosis on MRI (HS-ve) [2
]. Apart from the lack of evidence of the defining hippocampal sclerosis (HS) on MRI, HS-ve patients in general showed lateralised but more widespread temporal hypometabolism on FDG-PET with blinded visual assessment. This group were therefore dubbed "MRI negative PET positive TLE". Other findings in the HS-ve group included a less frequent history of febrile convulsions; slower rhythms at ictal EEG onset; less frequent histopathological hippocampal sclerosis, and a similarly good post surgical outcome even in the subgroup of HS-ve patients who had undergone a hippocampal sparing procedure. Further study with Statistical Parametric Mapping (SPM) has suggested the main difference between the groups lies in greater hippocampal hypometabolism in the HS+ve group [3
Brain volume deficits have been reported in epilepsies covering a range of syndromes and aetiologies, and to some extent can be used to differentiate these syndromes [4
]. Temporal lobe epilepsy in particular has been associated with regional and more widespread areas of atrophic change, sometimes only evident with detailed volumetric study [7
]. The most obvious structural difference between HS+ve and HS-ve temporal lobe epilepsy involves the presence or absence of hippocampal atrophy. However, an appreciation of more widespread differences in degree and distribution of volume deficits between these two groups, if present, may shed light on any possible pathophysiological differences.
The functional imaging characteristics of these groups are also of great interest. Many HS-ve patients, as with HS+ve patients, have prominent focal hypometabolism on FDG-PET scans [8
], with rare false lateralisation. The underlying pathophysiological basis for the hypometabolism seen in patients with TLE is still unresolved. While FDG-PET has shown a high correlation with MRI-identified HS for the lateralisation of the epileptogenic zone, many studies have found that the magnitude of the hypometabolism correlates weakly or not at all with either direct [9
] or indirect [10
](MRI hippocampal volumetry) measures of hippocampal neuronal loss, even in patients with HS. In both HS-ve and HS+ve TLE, decreased metabolism may involve lateral as well as mesial temporal structures. Our previous study suggested more extensive hypometabolism in HS-ve patients compared to HS+ve on blinded visual assessment, extending to more commonly involve temporal structures beyond anterior or mesial regions [2
]. However, the extent of differential involvement of temporal sub-regions and remote cortex on FDG-PET is difficult to quantitate visually.
Given the differences obvious on visual analysis, we were interested to investigate whether further differing patterns of structural or functional changes were present between these TLE subgroups using quantitative and semiquantitative methods. The primary hypothesis was that the epileptogenic focus in HS-ve patients involves primarily lateral rather than mesial temporal structures, and that the quantitative structural and functional changes would reflect this. The current study aimed to investigate this hypothesis by comparing volumetric MRI and coregistered FDG-PET metabolic measures on scans from HS+ve and HS-ve TLE patients.