Diffusion tensor imaging in medial temporal lobe epilepsy with hippocampal sclerosis

Abstract

Interictal diffusion imaging studies in patients with medial temporal lobe epilepsy (MTLE) accompanied by hippocampal sclerosis (HS) have shown an increased diffusivity in the epileptogenic hippocampus. In this study, we wanted to explore the whole brain in order to determine if MTLE could have an impact on the organization and the architecture of a large cerebral network and to identify clinical factors that could mediate diffusion abnormalities. Diffusion tensor imaging (DTI) and statistical parametric mapping of the entire brain were performed in 35 well-defined MTLE patients and in 36 healthy volunteers. SPM analyses identified three abnormal areas: an increased diffusivity was detected in the epileptic hippocampus and the ipsilateral temporal structures associated with a decreased anisotropy along the temporal lobe, a decreased diffusivity was found in the contralateral non-sclerotic hippocampus, the amygdala, and the temporal pole, and finally, a decreased anisotropy was noted ipsilaterally in posterior extratemporal regions. Duration of epilepsy, age at onset, and the frequency of generalized tonic–clonic seizures or partial complex seizures did not correlate with the presence of diffusion abnormalities. Region of interest analysis in the hippocampus/parahippocampus demonstrated a correlation between lower ipsilateral diffusivity values and occurrence of epigastric aura and between higher anisotropy values in both hemispheres and history of febrile seizures. In conclusion, this study showed that diffusion abnormalities are not restricted to the pathologic hippocampus and involve a larger network. This pattern may indirectly reflect the epileptogenic network and may be interpreted as a cause or a consequence of epilepsy.

Introduction

Diffusion tensor imaging (DTI) is an imaging technique which permits visualization of the architecture of cerebral tissue. The magnitude (diffusivity) and the directionality (anisotropy) of molecular displacement by diffusion can be quantified using DTI (Pierpaoli et al., 1996). In epilepsy patients, a decreased diffusivity was first reported in cases of both focal (Wieshmann et al., 1997, Lansberg et al., 1999) and non-convulsive status epilepticus (Flacke et al., 2000, Chu et al., 2001). Decreased diffusivity has also been observed inconsistently in the early post-ictal period following focal short-lasting seizures (Diehl et al., 2001, Hufnagel et al., 2003).

In medial temporal lobe epilepsy (MTLE) patients with hippocampal sclerosis (HS), interictal diffusion imaging studies (Hugg et al., 1999, Wieshmann et al., 1999, Kantarci et al., 2002, Assaf et al., 2003, Londono et al., 2003, Lee et al., 2004, Duzel et al., 2004) found an increased diffusivity in the hippocampal region ipsilateral to the side of seizure focus. The majority of these studies have focused on the sole hippocampus using regions of interest (ROIs) methods. Anyway, there is a growing evidence from electroclinical data that in MTLE, the epileptogenic onset zone, i.e., the medial temporal lobe, is expanded to incorporate a larger epileptic network, i.e., larger cortical or subcortical regions involved in seizure propagation or in seizures control (Nair et al., 2004, Deransart et al., 2000, Chauvel, 2001). Numerous neuroimaging studies have demonstrated that structural or functional abnormalities (metabolic changes, subtle structural lesions) may extend beyond the seizure onset zone in unilateral MTLE associated with HS (Duncan, 1997, Bernasconi et al., 2003, Moran et al., 2001, Woermann et al., 1999, Tasch et al., 1999) even though the exact physiopathology of these abnormalities is still unknown.

In this study, DTI combined with statistical parametric mapping allowed us to explore the entire brain and to gain further insight into the organization and the structure of cerebral tissue in well-defined MTLE. This method provided a way to characterize diffusion abnormalities in a large network. To better determine clinical factors that might influence diffusion abnormalities to be associated with MTLE, we specifically studied the influence of epilepsy duration, age at onset, frequency of generalized tonic–clonic seizures (GTCS), frequency of complex partial seizures (CPS), or history of febrile seizures (FS).