Whelan, Christopher D.;
Alhusaini, Saud;
O'Hanlon, Erik;
Cheung, Maria;
Iyer, Parames M.;
Meaney, James F.;
Fagan, Andrew J.;
Boyle, Gerard;
Delanty, Norman;
Doherty, Colin P.;
Cavalleri, Gianpiero L.
White matter alterations in patients with MRI‐negative temporal lobe epilepsy and their asymptomatic siblings
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Media type:
E-Article
Title:
White matter alterations in patients with MRI‐negative temporal lobe epilepsy and their asymptomatic siblings
Contributor:
Whelan, Christopher D.;
Alhusaini, Saud;
O'Hanlon, Erik;
Cheung, Maria;
Iyer, Parames M.;
Meaney, James F.;
Fagan, Andrew J.;
Boyle, Gerard;
Delanty, Norman;
Doherty, Colin P.;
Cavalleri, Gianpiero L.
Description:
<jats:title>Summary</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>The identification of “endophenotypes”—measurable variations along the pathways between genes and distal disease state—may help deconstruct focal epilepsies into more sensitive phenomena and improve future efforts to map the genetic underpinnings of the disorder. In this study, we set out to determine if diffusion tensor imaging (<jats:styled-content style="fixed-case">DTI</jats:styled-content>)–inferred white matter (<jats:styled-content style="fixed-case">WM</jats:styled-content>) alterations represent a suitable structural endophenotype for focal epilepsy.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We recruited 25 patients with sporadic mesial temporal lobe epilepsy (<jats:styled-content style="fixed-case">MTLE</jats:styled-content>) with normal magnetic resonance imaging (<jats:styled-content style="fixed-case">MRI</jats:styled-content>) findings, 25 of their gender‐matched, asymptomatic siblings, and 60 control subjects. Whole‐brain, voxelwise statistics were conducted to identify regions of microstructural degeneration in patients with <jats:styled-content style="fixed-case">MTLE</jats:styled-content> and/or their asymptomatic siblings. <jats:styled-content style="fixed-case">WM</jats:styled-content> tracts exhibiting evidence of microstructural disruption were then reconstructed using deterministic tractography. Diffusion metrics including fractional anisotropy (<jats:styled-content style="fixed-case">FA</jats:styled-content>) and mean diffusivity (<jats:styled-content style="fixed-case">MD</jats:styled-content>) were compared across groups using a series of one‐way multivariate analyses of covariance (<jats:styled-content style="fixed-case">MANCOVA</jats:styled-content>s).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Voxelwise statistics revealed significant <jats:styled-content style="fixed-case">FA</jats:styled-content> reductions in the corpus callosum (<jats:styled-content style="fixed-case">CC</jats:styled-content>), bilateral superior longitudinal fasciculi (<jats:styled-content style="fixed-case">SLF</jats:styled-content>), bilateral inferior longitudinal fasciculi (<jats:styled-content style="fixed-case">ILF</jats:styled-content>), and left corticospinal tract (<jats:styled-content style="fixed-case">CST</jats:styled-content>) in <jats:styled-content style="fixed-case">MTLE</jats:styled-content> patients only. <jats:styled-content style="fixed-case">MD</jats:styled-content> increases were observed in <jats:styled-content style="fixed-case">MTLE</jats:styled-content> patients and their asymptomatic siblings in the left <jats:styled-content style="fixed-case">SLF</jats:styled-content> and left <jats:styled-content style="fixed-case">CST</jats:styled-content>. Deterministic tractography supported the voxelwise results, revealing significant <jats:styled-content style="fixed-case">FA</jats:styled-content> alterations in the left <jats:styled-content style="fixed-case">SLF</jats:styled-content> and <jats:styled-content style="fixed-case">CST</jats:styled-content> in patients only and significant <jats:styled-content style="fixed-case">MD</jats:styled-content> alterations in <jats:styled-content style="fixed-case">MTLE</jats:styled-content> patients and their unaffected siblings. The diffusion scalars of <jats:styled-content style="fixed-case">MTLE</jats:styled-content> patients and their asymptomatic siblings were highly correlated in the <jats:styled-content style="fixed-case">SLF</jats:styled-content> and <jats:styled-content style="fixed-case">CST</jats:styled-content> ipsilateral to patients' sides of seizure onset.</jats:p></jats:sec><jats:sec><jats:title>Significance</jats:title><jats:p>These findings confirm the presence of microstructural <jats:styled-content style="fixed-case">WM</jats:styled-content> alterations in patients with <jats:styled-content style="fixed-case">MRI</jats:styled-content>‐negative <jats:styled-content style="fixed-case">MTLE</jats:styled-content> and provide preliminary support for a diffusion‐based endophenotype in the disorder. Further studies of narrow‐sense heritability in larger cohorts of first‐degree relatives of <jats:styled-content style="fixed-case">MTLE</jats:styled-content> patients are required to confirm these results.</jats:p></jats:sec>