Alterations In The Hippocampal-thalamic Pathway Underlying Secondarily Generalized Tonic-clonic Seizures In Mesial Temporal Lobe Epilepsy

Objective:The epileptogenic network underlying secondarily generalized tonic-clonic seizures(sGTCS)in mesial temporal lobe epilepsy(mTLE)is not well understood.Here,we investigated alterations in the probabilistic hippocampal-thalamic pathway(HTP)underlying sGTCS using diffusion tensor imaging in a cohort of mTLE patients with hippocampal sclerosis(HS).Methods:We consecutively recruited 51 unilateral mTLE-HS patients(26 with and 25 without sGTCS)and 22 healthy controls.All participates accepted high-resolution three-dimensional sagittal T1-weighted brain volume imaging and diffusion tensor imaging scanning.Probabilistic tractography was used to track the HTP.Raw fractional anisotropy(FA)and mean diffusivity(MD)of the HTP were corrected by the FA/MD of the hemispheric white matter on the same side.The volume of the thalamic subregion connected to the hippocampus(TSCH)were investigated.Results:After correction,the sGTCS group showed lower FA than the non-sGTCS group(P=0.03),and lower FA as well as higher MD than controls in the ipsilateral HTP.The non-sGTCS group only showed higher corrected MD in the ipsilateral HTP relative to controls.Corrected FA or MD in the contralateral HTP did not differ among the three groups.The TSCH was located in the mesial aspect of the thalamus.The ipsilateral TSCH was atrophied in the sGTCS group compared to the non-sGTCS group and controls.The volume of contralateral TSCH did not differ among the three groups.Conclusions:In TLE-HS,sGTCS was associated with impaired integrity of the HTP as well as structural atrophy in the medial thalamus.The HTP and medial thalamus may be important in seizure generalization in mTLE.