Abstracts

Data from mTLE patients have shown abnormalities in FDG uptake in the subcortical nuclei which have been correlated to dentate and hilar cell loss. While the CMRglc is a sensitive evaluation for rate of substrate use, the tissue[apos]s current bioenergetic state can be directly assessed with 31P spectroscopy. Previously bioenergetic abnormalities have been seen with 31P spectroscopic imaging in the hippocampus and used in the lateralization of epileptogenic regions. In this report we correlated regional 31P spectroscopic imaging data for bioenergetic state in relation to post-operative histopathology in n=14 unilateral mTLE patients.
Three dimensional 31P MR spectroscopic imaging was performed at 4Tesla in patients and controls (n=14). Regions studied included the bilateral hippocampi (amygdala, pes hippocampus, hippocampal body), thalamus and striatum. Bioenergetic impairment was determined by the phosphocreatine to ATP ratio (PCr/ATP), and evaluated in relation to clinical and neuropathologic evaluation of hippocampal glial fibrillary acidic protein (GFAP) staining, gliosis and neuronal loss.
Cross-hemispherically, the ipsilateral thalamic PCr/ATP correlated significantly with the contralateral hippocampal PCr/ATP (R=0.55, p[lt]0.02). The ipsilateral thalamus also significantly correlated with dentate GFAP staining (R= -0.60, p[lt]0.02, Fig. 1) while the bilateral striate PCr/ATP related significantly to CA1 GFAP staining (R= -0.57, p[lt]0.03 ipsi; R= -0.60, p[lt]0.02 contra; data not shown). Correlation of the striatal PCr/ATP to dentate GFAP staining revealed a logarithmic dependence, which was significant with R=0.70, p[lt]0.005, Fig. 1,2).
GFAP expression is known to be induced with repetitive seizures and is elevated in chronic epilepsy. The bioenergetic data also likely reflects acute seizure occurrence and inter-ictal spike spread. Based on the neuropathology in mTLE where dentate mossy fiber axons [rarr] CA3 [rarr] CA1, the imaging correlations with GFAP staining suggest that bioenergetically, the ipsilateral thalamus functions upstream with the dentate while the bilateral striate functions downstream with CA1. This multi-step connectivity may also contribute to the non-linear dependence of dentate GFAP staining seen with striate energetics. These data support a view wherein a network of bioenergetic impairment is seen in unilateral TLE, involving the hippocampus, thalamus and striatum. In particular, the extent and distribution of energetic insufficiency appears to depend on the varying components of damage in the ipsilateral hippocampus.[figure1]
[Supported by: NIH NINDS P01 39092, R01 40550, Charles A Dana Foundation]