Abstract
Temporal lobe epilepsy (TLE) is associated with brain pathology extending beyond temporal lobe structures. We sought to look for informative patterns of brain tissue properties in TLE that go beyond the established morphometry differences. We hypothesised that volume differences, particularly in hippocampus, will be paralleled by changes in brain microstructure. The cross-sectional study included TLE patients (n = 25) from a primary care center and sex-/age-matched healthy controls (n = 55). We acquired quantitative relaxometry-based magnetic resonance imaging (MRI) data yielding whole-brain maps of grey matter volume, magnetization transfer (MT) saturation, and effective transverse relaxation rate R2* indicative for brain tissue myelin and iron content. For statistical analysis, we used the computational anatomy framework of voxel-based morphometry and voxel-based quantification. There was a positive correlation between seizure activity and MT saturation measures in the ipsilateral hippocampus, paralleled by volume differences bilaterally. Disease duration correlated positively with iron content in the mesial temporal lobe, while seizure freedom was associated with a decrease of iron in the very same region. Our findings demonstrate the link between TLE clinical phenotype and brain anatomy beyond morphometry differences to show the impact of disease burden on specific tissue properties. We provide direct evidence for the differential effect of clinical phenotype characteristics on processes involving tissue myelin and iron in mesial temporal lobe structures. This study offers a proof-of-concept for the investigation of novel imaging biomarkers in focal epilepsy.
Highlights
There is mounting evidence for brain pathology extending beyond the temporal lobe in patients with temporal lobe epilepsy (TLE)—one of the most common forms of focal epilepsy
The handedness (p = 0.54) and sex distribution (p = 0.34) of TLE patients were comparable to healthy controls
We report a larger hippocampal volume bilaterally in TLE patients, to operculum bilaterally, ipsilateral middle temporal gyrus and contralateral cerebellar and postcentral regions (Fig. 1, Table 2A)
Summary
There is mounting evidence for brain pathology extending beyond the temporal lobe in patients with temporal lobe epilepsy (TLE)—one of the most common forms of focal epilepsy. Under the supposition of seizureinduced neurogenesis rate increase, evidence from animal models shows that newly generated neuronal granule cells migrate into the hilus as far as the hippocampal CA3, where due to abnormal integration into hippocampal networks they start contributing to recurrent excitatory circuits (Scharfman et al 2000). This seizure-related aberrant network development is followed by hippocampal myelin loss and fiber degeneration in TLE, especially for small diameter axons, demonstrated by animal models and post mortem investigations (Ozdogmus et al 2009). Supported by findings showing epilepsy-associated changes of hilar ectopic granule cells (Scharfman et al 2000) paralleled by changes in myelinated fibers (Luo et al 2015; Ye et al 2013), myelin-sensitive neuroimaging techniques would allow to probe microstructural tissue differences in TLE patients
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