Metabolic changes and electro‐clinical patterns in mesio‐temporal lobe epilepsy: a correlative study

DOI: 10.1093/brain/awh014 Advanced Access publication October 8, 2003 Brain (2004), 127, 164±174 Metabolic changes and electro-clinical patterns in mesio-temporal lobe epilepsy: a correlative study Francine Chassoux,1,2 Franck Semah,2 Viviane Bouilleret,2 Elisabeth Landre,1 Bertrand Devaux,1 Baris Turak,1 FrancËois Nataf1 and FrancËois-Xavier Roux1 1Department of Neurosurgery, Centre Hospitalier SainteAnne, Paris and 2SHFJ, CEA, Orsay, France Summary Interictal hypometabolism is commonly found in mesiotemporal lobe epilepsy (MTLE), but its pathophysiology remains incompletely understood. We hypothesized that metabolic changes re¯ect the preferential networks involved by ictal discharges. We analysed the topography of interictal hypometabolism according to electro-clinical patterns in 50 patients with unilateral hippocampal sclerosis (HS) and consistent features of MTLE. Based on electro-clinical correlations, we identi®ed four groups: (i) mesial group (13 cases) characterized by mesial seizure onset without evidence of early spread beyond the temporal lobe; (ii) anterior mesiolateral group (AML; 18 cases) with early anterior spread involving the anterior lateral temporal cortex and insulo-fronto-opercular areas; (iii) widespread mesio-lateral group (WML; 15 cases) with wide spread (involving both anterior and posterior lateral temporal and perisylvian areas); and (iv) bitemporal (BT) group (four cases) with early contralateral temporal spread. Results of [18F]¯uorodeoxyglucose-PET imaging in each group were compared with those of 10 control subjects using statistical parametric mapping software (SPM99). Correspondence to: Francine Chassoux, MD, Department of Neurosurgery, Sainte-Anne Hospital, 1 rue Cabanis, 75014 Paris, France E-mail: MRI data and surgical outcome in each group were compared with metabolic ®ndings. Hypometabolism was limited to hippocampal gyrus, temporal pole and insula in the mesial group. Gradual involvement of lateral temporal cortex, insula and perisylvian areas was observed in the AML and WML groups. The BT group differed from the others with mild bitemporal involvement, bilateral insular hypometabolism and longer epilepsy duration. MRI structural abnormalities outside of the mesial formations were detected in 65% of the cases. Neither the severity of HS nor temporal atrophy appeared related to the topography of hypometabolism. However, temporal hypometabolism was more extended when temporo-polar signal changes were detected. Among operated patients (n = 43), seizure-free outcome was obtained in 82%. Surgical outcome appeared more favourable in the mesial group. However, the difference between the four groups was not signi®cant. Our results suggest that hypometabolism in MTLE may be related to ictal discharge generation and spread pathways, even if structural changes and epilepsy duration may also play a role. Keywords: mesio-temporal lobe epilepsy; hippocampal sclerosis; EEG; cerebral metabolism; epilepsy surgery Abbreviations: AML = anterior mesio-lateral; BT = bitemporal; [18F]FDG = ¯uorodeoxyglucose; FLAIR = ¯uid attenuation inversion recovery; HS = hippocampal sclerosis; MTLE = mesio-temporal lobe epilepsy; SEEG = stereoelectroencephalography; SPM = statistical parametric mapping; WML = widespread mesio-lateral Introduction Mesio-temporal lobe epilepsy (MTLE) is a localizationrelated syndrome identi®ed during the last decade. Its identi®cation has proven to be valuable for epilepsy surgery candidate selection. Diagnosis is based on a combination of past history (in particular complicated febrile convulsions), clinical presentation (complex partial seizures with vegetative aura), EEG (anterior temporal focus) and imaging ®ndings (hippocampal sclerosis; HS) (French et al., 1993; Wieser et al., 1993; Williamson et al., 1993; Mathern et al., 1995; Engel, 1996). The place of PET imaging in MTLE diagnosis and determining surgical prognosis has largely been demonstrated (Engel et al., 1982a; Theodore et al., 1992; Hajek et al., 1993; Henry et al., 1993; Radtke et al., 1993; Spencer, 1994). MTLE has proven to be one of the most medically refractory localization-related epilepsy syndromes (Semah et al., 1998). It is now considered as the prototype of a surgically Brain Vol. 127 No. 1 ã Guarantors of Brain 2003; all rights reserved Metabolic patterns in MTLE remediable syndrome (Engel, 1998). However, so-called MTLE does not appear to be homogeneous from an electroclinical point of view (Adam et al., 1996; Bartolomei et al., 1999). Moreover, recent studies have indicated involvement of structures beyond the limits of the mesial temporal area, particularly of the temporal pole (Mitchell et al., 1999) and insular cortex (Isnard et al., 2000; Bouilleret et al., 2002). In addition, widespread structural brain abnormalities associated with HS have been demonstrated (Sisodiya et al., 1997; Moran et al., 2001). Failure after anterior temporal resection in some patients also suggests that the epileptogenic zone is not always con®ned to mesial structures (Hennessy et al., 2000). These observations provide some evidence that the hippocampus, even though it is characterized by a lower threshold for seizure generation, is part of a larger regional epileptogenic network involving neocortical temporal cortex and extra-temporal areas. The organization of this network may differ from one patient to another despite an apparently identical seizure onset zone, but seems individually ®xed, consistent with the observation that ictal semeiology remains remarkably stereotyped for a given patient. Whether cerebral metabolism studies provide further information about the neuronal network involved in MTLE remains open to debate. Interictal temporal hypometabolism ipsilateral to the epileptic focus is detected in 80±97% of MTLE cases (Spencer, 1994; Semah et al., 1995; Adam et al., 1996; Ryvlin et al., 1998). However, various patterns in temporal and extra-temporal areas have been reported. Hypometabolism is usually much larger than the structural lesion and epileptogenic zone (Engel et al., 1982b; Sackellares et al., 1990; Ryvlin et al., 1991; Theodore et al., 1992; Hajek et al., 1993; Henry et al., 1993) and often spreads over extra-temporal cortical areas including subcortical structures (Arnold et al., 1996; Savic et al., 1997; Dupont et al., 1998). Despite intensive studies during the last two decades, the pathophysiology of interictal hypometabolism and its clinical relevance remain incompletely understood. It has been postulated that structural changes may account for hypometabolism mechanisms, but a strong relationship has failed to be demonstrated. Recent studies demonstrate that the topography of the hypometabolism may be related to brain areas which generate the clinical expression of ictal onset and spread (Savic et al., 1997; Dupont et al., 1998; Koutroumanidis et al., 2000). We hypothesized that interictal hypometabolism re¯ects the preferential (...truncated)