  Objective: To identify if whole-brain structural network alterations in
patients with temporal lobe epilepsy (TLE) and focal to bilateral tonic-clonic
seizures (FBTCS) differ from alterations in patients without FBTCS.
  Methods: We dichotomized a cohort of 83 drug-resistant patients with TLE into
those with and without FBTCS and compared each group to 29 healthy controls.
For each subject, we used diffusion MRI to construct whole-brain structural
networks. First, we measured the extent of alterations by performing
FBTCS-negative (FBTCS-) versus control and FBTCS-positive (FBTCS+) versus
control comparisons, thereby delineating altered sub-networks of the
whole-brain structural network. Second, by standardising networks of each
patient using control networks, we measured the subject-specific abnormality at
every brain region in the network, thereby quantifying the spatial localisation
and the amount of abnormality in every patient.
  Results: Both FBTCS+ and FBTCS- patient groups had altered sub-networks with
reduced fractional anisotropy (FA) and increased mean diffusivity (MD) compared
to controls. The altered subnetwork in FBTCS+ patients was more widespread than
in FBTCS- patients (441 connections altered at t>3, p<0.001 in FBTCS+ compared
to 21 connections altered at t>3, p=0.01 in FBTCS-). Significantly greater
abnormalities-aggregated over the entire brain network as well as assessed at
the resolution of individual brain areas-were present in FBTCS+ patients
(p<0.001, d=0.82). In contrast, the fewer abnormalities present in FBTCS-
patients were mainly localised to the temporal and frontal areas.
  Significance: The whole-brain structural network is altered to a greater and
more widespread extent in patients with TLE and FBTCS. We suggest that these
abnormal networks may serve as an underlying structural basis or consequence of
the greater seizure spread observed in FBTCS.
