Progression of Brain Damage after Status Epilepticus and Its Association with Epileptogenesis: A Quantitative MRI Study in a Rat Model of Temporal Lobe Epilepsy

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Abstract
Summary: Purpose: This study examined the hypothesis that neurodegeneration continues after status epilepticus (SE) ends and that the severity of damage at the early phase of the epileptogenic process predicts the outcome of epilepsy in a long-term follow-up. Methods: SE was induced in rats by electrical stimulation of the amygdala, and the progression of structural alterations was monitored with multiparametric magnetic resonance imaging (MRI). Absolute T2, T1ρ, and diffusion (Dav) images were acquired from amygdala, piriform cortex, thalamus, and hippocampus for ≤4.5 months after SE. Frequency and type of spontaneous seizures were monitored with video-electroencephalography recordings. Histologic damage was assessed from Nissl, Timm, and Fluoro-Jade B preparations at 8 months. Results: At the acute phase (2 days after SE induction), quantitative MRI revealed increased T2, T1ρ, and Dav values in the primary focal area (amygdala), reflecting disturbed water homeostasis and possible early structural damage. Pathologic T2 and T1ρ were observed in mono- or polysynaptically connected regions, including the piriform cortex, midline thalamus, and hippocampus. The majority of acute MRI abnormalities were reversed by 9 days after SE. In later time points (>20 days after induction), both the T1ρ and diffusion MRI revealed secondarily affected areas, most predominantly in the amygdala and hippocampus. At this time, animals began to have spontaneous seizures. The initial pathology revealed by MRI had a low predictive value for the subsequent severity of epilepsy and tissue damage. Conclusions: The results demonstrate progressive neurodegeneration after SE in the amygdala and the hippocampus and stress the need for continued administration of neuroprotectants in the treatment of SE even after electrographic seizure activity has ceased.