Epilepsy-related cytoarchitectonic abnormalities along white matter pathways

Glenn, G. Russell; Jensen, Jens H.; Helpern, Joseph A.; Spampinato, Maria Vittoria; Kuzniecky, Ruben; Keller, Simon S.; Bonilha, Leonardo

doi:10.1136/jnnp-2015-312980

Cited by 28 publications

(43 citation statements)

References 38 publications

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“…Interestingly, we found that MD is more sensitive than FA in determining differences between patients versus controls and is able to detect extensive bilateral effects. These findings are consistent with those reported in other studies that have employed within-tract analyses to demonstrate increased alterations in MD in patients with mesial TLE (Concha et al, 2012, Glenn et al, 2016), although similar findings have not been reported in patients with cryptogenic TLE (Keller et al, 2013). The inconsistencies may in part be explained by different types of analysis approaches, as, for example, a tract-based approach has been shown to be more sensitive than voxel-based ones (Focke et al, 2008).…”

Section: Discussionsupporting

confidence: 92%

“…Information obtained from whole-tract analyses are limited because there may be significant variations in diffusion characteristics along the length of white matter tracts (Johnson et al, 2013), and it is likely that some pathological tract alterations occur in circumscribed regions within tracts and not along entire tracts in patients with TLE. Therefore it is important to develop methods that permit analysis of within-tract tissue characteristics in patients with TLE (Concha et al, 2012, Glenn et al, 2016). In the present study, we sought to apply TRACULA methods to investigate within-tract alterations in TLE, and to determine whether these regional alterations are influenced by the extent of hippocampal atrophy and clinical variables.…”

Section: Introductionmentioning

confidence: 99%

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Automated tractography in patients with temporal lobe epilepsy using TRActs Constrained by UnderLying Anatomy (TRACULA)

Kreilkamp

Weber

Richardson

et al. 2017

NeuroImage: Clinical

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PurposeA detailed understanding of white matter tract alterations in patients with temporal lobe epilepsy (TLE) is important as it may provide useful information for likely side of seizure onset, cognitive impairment and postoperative prognosis. However, most diffusion-tensor imaging (DTI) studies have relied on manual reconstruction of tract bundles, despite the recent development of automated techniques. In the present study, we used an automated white matter tractography analysis approach to quantify temporal lobe white matter tract alterations in TLE and determine the relationships between tract alterations, the extent of hippocampal atrophy and the chronicity and severity of the disorder.MethodsWe acquired preoperative T1-weighted and DTI data in 64 patients with well-characterized TLE, with imaging and histopathological evidence of hippocampal sclerosis. Identical acquisitions were collected for 44 age- and sex-matched healthy controls. We employed automatic probabilistic tractography DTI analysis using TRActs Constrained by UnderLying Anatomy (TRACULA) available in context of Freesurfer software for the reconstruction of major temporal lobe tract bundles. We determined the factors influencing probabilistic tract reconstruction and investigated alterations of DTI scalar metrics along white matter tracts with respect to hippocampal volume, which was automatically estimated using Freesurfer's morphometric pipelines. We also explored the relationships between white matter tract alterations and duration of epilepsy, age of onset of epilepsy and seizure burden (defined as a function of seizure frequency and duration of epilepsy).ResultsWhole-tract diffusion characteristics of patients with TLE differed according to side of epilepsy and were significantly different between patients and controls. Waypoint comparisons along each tract revealed that patients had significantly altered tissue characteristics of the ipsilateral inferior-longitudinal, uncinate fasciculus, superior longitudinal fasciculus and cingulum relative to controls. Changes were more widespread (ipsilaterally and contralaterally) in patients with left TLE while patients with right TLE showed changes that remained spatially confined in ipsilateral tract regions. We found no relationship between DTI alterations and volume of the epileptogenic hippocampus. DTI alterations of anterior ipsilateral uncinate and inferior-longitudinal fasciculus correlated with duration of epilepsy (over and above effects of age) and age at onset of epilepsy. Seizure burden correlated with tissue characteristics of the uncinate fasciculus.ConclusionThis study shows that TRACULA permits the detection of alterations of DTI tract scalar metrics in patients with TLE. It also provides the opportunity to explore relationships with structural volume measurements and clinical variables along white matter tracts. Our data suggests that the anterior temporal lobe portions of the uncinate and inferior-longitudinal fasciculus may be particularly vulnerable to pathological alterations...

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Automated tractography in patients with temporal lobe epilepsy using TRActs Constrained by UnderLying Anatomy (TRACULA)

Kreilkamp

Weber

Richardson

et al. 2017

NeuroImage: Clinical

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“…This finding was demonstrated in both our voxelwise and tract-based analysis and is commensurate with a small, but growing literature demonstrating improved sensitivity of advanced diffusion imaging for delineating white matter pathology in epilepsy. Similar to studies indicating that DKI-derived measures (e.g., mean kurtosis) may provide a more sensitive measure of pathology 10; 12; 28–30 , we found the pattern of reduced ND to be more robust and congruent with known network abnormalities in TLE, which are most prominent within medial temporal/limbic networks ipsilateral and proximal to the seizure focus 5 (Figure 3). However, it is important to note that whereas reduced kurtosis indicates a loss of diffusion heterogeneity—a metric that should correlate with a loss of diffusion restriction, and therefore, white matter pathology—RSI is a multi-compartment model that can more directly probe the nature of this pathology.…”

Section: Discussionsupporting

confidence: 86%

Restriction spectrum imaging reveals decreased neurite density in patients with temporal lobe epilepsy

et al. 2016

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Objective Diffusion tensor imaging (DTI) has become a popular tool for delineating the location and extent of white matter injury in temporal lobe epilepsy (TLE). However, DTI yields nonspecific measures that are confounded by changes occurring within both the intracellular and extracellular environments. This study investigated whether an advanced diffusion method, restriction spectrum imaging (RSI) could provide a more robust measure of white matter injury in TLE relative to DTI due to RSI’s ability to separate intra-axonal diffusion (i.e., neurite density; ND) from diffusion associated with extra-axonal factors (e.g., inflammation; crossing fibers). Methods RSI and DTI scans were obtained on 21 patients with TLE and 11 age-matched controls. RSI-derived maps of ND, isotropic hindered (IH) and free (IF) water, and crossing fibers (CF) were compared to DTI-derived fractional anisotropy (FA) maps. Voxelwise and tract-based analyses were performed comparing patients with TLE to controls on each diffusion metric. Results Reductions in FA were seen primarily in frontotemporal white matter in TLE and were most pronounced proximal to the seizure focus. Reductions in ND corresponded to those seen in the FA maps; however, ND reductions were greater in magnitude, more lateralized to the epileptogenic hemisphere, and showed a broader pattern. Increases in IF/IH and effects from CFs also contributed to reduced FA in the ipsilateral parahippocampal cingulum and fornix, with decreases in IH extending into extratemporal regions. Reduced ND of the uncinate fasciculus was associated with longer disease duration, whereas FA was not associated with any clinical variables. Significance RSI may provide a more specific measure of white matter pathology in TLE, distinguishing regions primarily affected by axonal/myelin loss from those where CFs and increases in extracellular water also play a role. By providing a more specific measure of axonal/myelin loss, RSI-derived ND may better reflect overall white matter burden in epilepsy.

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“…Lower tract identification rates in the fimbria-fornix may be attributable to the curvature of the tract or contributions of multiple fibre bundle orientations in complex neural tissue (Johnson et al , 2013). These limitations can potentially be overcome with improved image quality (Johnson et al , 2013) or higher order diffusion techniques (Glenn et al , 2016), which can both augment the performance AFQ. Despite the failed reconstruction of fimbria-fornix bundles in a minority of subjects causing a small reduction in our sample size for analysis, we have demonstrated highly significant differences between outcome groups in this region corrected for multiple comparisons in group comparison studies, and as a potential outcome classifier using ROC curves.…”

Section: Discussionmentioning

confidence: 99%

“…For segmentation of the fimbria-fornix, we implemented an in-house algorithm using AFQ’s routine [see Supplementary material and Glenn et al (2016)]. Each fibre bundle was interpolated along 100 sections and along-the-tract profiles were reconstructed for mean diffusivity and fractional anisotropy for both left- and right-sided pathways.…”

Section: Methodsmentioning

confidence: 99%

Preoperative automated fibre quantification predicts postoperative seizure outcome in temporal lobe epilepsy

Keller

Glenn

Weber

et al. 2016

Brain

Self Cite

107

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Epilepsy-related cytoarchitectonic abnormalities along white matter pathways

Cited by 28 publications

References 38 publications

Automated tractography in patients with temporal lobe epilepsy using TRActs Constrained by UnderLying Anatomy (TRACULA)

Automated tractography in patients with temporal lobe epilepsy using TRActs Constrained by UnderLying Anatomy (TRACULA)

Restriction spectrum imaging reveals decreased neurite density in patients with temporal lobe epilepsy

Preoperative automated fibre quantification predicts postoperative seizure outcome in temporal lobe epilepsy

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