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Corpus callosum involvement in mesial temporal lobe epilepsy and non lesional frontal lobe epilepsy: a multimodal MRI study1Neuroscience Research Center, University Magna Graecia of Catanzaro, Catanzaro, Italy, 2Neuroimaging Unit, Institute of Molecular Bioimaging and Physiology, National Research Council (IBFM-CNR), Catanzaro, Italy, 3Institute of Neurology, University Magna Graecia of Catanzaro, Catanzaro, Italy
Synopsis
Mesial Temporal Lobe Epilepsy (MTLE) and Frontal Lobe Epilepsy (FLE) are the two most common forms of partial epilepsy. While MTLE has been widely studied, FLE has been less investigated. Patients with FLE in which there is no clearly identifiable abnormality on MRI (non lesional FLE, nlFLE) represent an ideal sample to study the epileptic syndrome itself, regardless of the nature and location of the epileptogenic focus in the frontal lobe. Here, we studied the involvement of the corpus callosum in temporal and frontal lobe epilepsy, considering non-lesional FLE, refractory MTLE and mild MTLE, a particularly drug-responsive phenotype. Neuroimaging characteristics of CC seem to be indeed altered with patterns that are specific to the different epileptic syndromes.
Introduction
Mesial Temporal Lobe Epilepsy (MTLE) and Frontal Lobe Epilepsy (FLE) are the two most common forms of partial epilepsy. While MTLE has been widely described and studied using magnetic resonance imaging (MRI) techniques, FLE has been less investigated. In FLE patients, seizure onset is usually caused by a lesion or by a cortical dysplasia. This leads to great variability in the brain characteristics of patients, raising issues in identifying homogeneous samples for neuroimaging studies. However, some patients with FLE can be defined non lesional (nlFLE), i.e., seizures start in the frontal lobe, but there is no clearly identifiable abnormality on MRI. For this reason, nlFLE patients represent an ideal sample for the study of the epileptic syndrome itself, regardless of the nature and location of the epileptogenic focus in the frontal lobe. Several studies have recently demonstrated that white matter involvement might be a biomarker of drug-resistance in MTLE; more in detail, it has been demonstrated that corpus callosum (CC) thickness and microstructure are altered in refractory MTLE (rMTLE), while they seems to be spared in mild MTLE, a particularly drug-responsive syndrome characterized by very well controlled seizures1,2. Here, we aimed at investigating the integrity of CC in nlFLE and MTLE, with the hypothesis that its neuroimaging characteristics might be altered in regions specific to different epileptic syndromes.
Methods
The study group included 79 patients with mMTLE (54 female; mean age ± standard deviation [SD] 43.2 ± 14.8 years), 61 with rMTLE (32 female; mean age ± SD 45.2 ± 12.4 years), 20 nlFLE (10 female; mean age ± SD 38.0 ± 18.9 years) and 134 healthy controls (HC, 73 female; mean age ± SD 44.8 ± 15.5 years). All subjects underwent a 3T MRI protocol including whole-brain, 3D FSPGR T1-weighted images (TI/TE/TR = 650/3.7/9.2 ms; flip angle=12°; number of slices 184; no slice-gap; voxel size 1x1x1mm3), DTI (TE/TR=83.9/9750 ms; b=0,1000; diffusion-weighting along 27 non-collinear gradient directions; matrix size 128x128; 80 axial slices; number of b0 images=4; NEX=2; voxel size 2x2x2mm3) and conventional FLAIR. DTI and T1 scans were combined to measure thickness, mean diffusivity (MD) and fractional anisotropy (FA) over 50 regions of interest along the cross-sectional CC profile2-3. Differences in MRI metrics at each node across groups were assessed by an analysis of variance (ANOVA) with gender, age and disease duration included as potential confounding factors. Tukey’s post-hoc test was used for multiple-comparisons-corrected pairwise contrasts. Significance threshold was set at 0.05. Since no a priori subdivision was used for the CC, Witelson’s scheme4 served as a guide to interpret results (Figure 1).Results
Figure 1 shows CC regions where significant differences were found across groups. Patients with mMTLE did not differ from HC. Patients with rMTLE had all imaging metrics of posterior CC altered compared to HC and mMTLE. Decreased thickness and FA in the anterior CC (Witelson's sections 1-2) were also found in rMTLE compared to controls, whereas MD was increased in CC genu (section 1) of rMTLE vs HC only. Patients with nlFLE compared to HC showed altered imaging metrics in CC genu and reduced thickness in Witelson's section 5. Compared to mMTLE, instead, nlFLE showed almost no significant difference, with the exception of a small region of significantly increased MD in the genu. Patients with rMLTE compared to those with nlFLE showed decreased thickness in the genu and decreased FA in Witelson's section 4.
Discussion
The involvement of posterior CC in rMTLE is in line with the fact that this portion of the bundle is crossed by fibers connecting the temporal lobes. In these drug-resistance patients, seizures start in the temporal lobe and spread throughout the brain, possibly altering microstructure of other regions, which in turn would explain the involvement of more anterior CC regions. At the same time, the good control of seizures in mMTLE explains the lack of alterations in these patients compared to controls. For what concerns nlFLE, patients showed altered characteristics of anterior CC, in line with the site of the epileptogenic focus in the frontal lobe. Alterations in rMTLE compared to nlFLE might be explained by the fact that the former group comprises patients undertaking multiple anti-epileptic drugs, which might induce changes in brain structure.Conclusion
Our results support the hypothesis that white matter alterations are indeed crucial in the development of epileptic syndromes and drug-resistance. Further studies are needed to better untangle if white matter involvement is indeed a congenital susceptibility factor, or if it is influenced by the frequency of seizures and by the combination of multiple anti-epileptic drugs.Acknowledgements
No acknowledgement found.References
1. Labate A, Aguglia U, Tripepi G, et al., Long-term outcome of mild mesial temporal lobe epilepsy. Neurology 2016; 86(20):1904-1910.
2. Caligiuri ME, Labate A, Cherubini A, et al., Integrity of the corpus callosum in patients with benign temporal lobe epilepsy. Epilepsia 2016;57:590- 596.
3. Adamson CL, Wood AG, Chen J, et al., Thickness profile generation for the corpus callosum using Laplace’s equation. Hum Brain Mapp 2011; 32:2131-2140.
4. Witelson, S.F., Hand and sex differences in the isthmus and genu of the human corpus callosum. A postmortem morphological study, Brain 1989; 112:799–835.
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