Network evolution in mesial temporal lobe epilepsy revealed by diffusion tensor imaging

Abstract

OBJECTIVE The objective of the present study is to identify novel, time-indexed imaging biomarkers of epileptogenesis in mesial temporal lobe epilepsy (MTLE). METHODS We used high-resolution brain diffusion tensor imaging (DTI) of the translationally relevant methionine sulfoximine (MSO) brain infusion model of MTLE. MSO inhibits astroglial glutamine synthetase, which is deficient in the epileptogenic hippocampal formation of patients with MTLE. MSO-infused (epileptogenic) rats were compared with phosphate buffered saline (PBS)-infused (nonepileptogenic) rats at early (3–4 days) and late (6–9 weeks) time points during epileptogenesis. RESULTS The epileptogenic rats exhibited significant changes in DTI-measured fractional anisotropy (FA) in numerous brain regions versus nonepileptogenic rats. Changes included decreases and increases in FA in regions such as the entorhinal-hippocampal area, amygdala, corpus callosum, thalamus, striatum, accumbens and neocortex. The FA changes evolved over time as animals transitioned from early to late epileptogenesis. For example, some areas with significant decreases in FA early in epileptogenesis changed to significant increases late in epileptogenesis. Finally, the FA changes significantly correlated with the seizure load. SIGNIFICANCE Our results suggest (a) that high resolution DTI can be used for early identification and tracking of the epileptogenic process in MTLE, and (b) that the process identified by DTI is present in multiple brain areas, even though infusion of MSO is restricted to the unilateral entorhinal-hippocampal region.

Abnormal Brain Network in Epilepsy and Associated Comorbidites

“…This change is related to the duration of epilepsy, and the white matter pathway is easily influenced by seizure recurrence. Similar findings were observed in animal model of mTLE [10]. The epileptogenic rats exhibited significant changes in DTI-measured fractional anisotropy (FA) in numerous brain regions versus nonepileptogenic rats.…”

“…In previous studies on structural network abnormalities in epilepsy with cognitive impairment, Volumetric MRI and VBM have revealed significant volume losses in the area of the seizure focus as well as in distant areas [53,54]. DTI adds evidence of loss of integrity of connections from the seizure focus to distant areas as well as between distant areas [10,55]. A study [52] collected DTI data from 39 patients with nonsymptomatic localization--related epilepsy and varying degrees of cognitive impairment and 23 age-matched healthy controls.…”

Connectivity‐based parcellation of the nucleus accumbens into core and shell portions for stereotactic target localization and alterations in each NAc subdivision in mTLE patients

“…Parekh et al () found changes in FA in the hippocampus, amygdala, entorhinal cortex, piriform cortex, and thalamus in a limbic status epilepticus model of epileptogenesis. Wang et al () investigated decreases and increases in FA in regions such as the entorhinal‐hippocampal area, amygdala, thalamus, striatum, accumbens, and neocortex in methionine sulfoximine‐infused rats as model of human MTLE. Peng et al () observed altered diffusion parameters of subcortical gray matter in patients with MRI‐negative cortical epilepsy using DTI, and reported the decrease in FA values in the bilateral nucleus accumbens in epilepsy patients for the first time.…”

“…The decreases in FA using DTI are known to occur in gray matter areas during cerebral ischemia and sustained seizures. Such decreases in FA are thought to reflect blood–brain barrier disruption with cytotoxic edema and contraction of the extracellular space volume (Wang et al, ).…”

“…Most prior studies using DTI reveal changes preferentially in white matter structures, which reflect axonal number, membrane circumference, and myelin thickness information in white matter. However, with cytotoxic edema and contraction of the extracellular space volume (Wang et al, 2017).…”