Objective The present study is aimed at characterizing the different diffusion alterations between patients with partial seizure(PS) and secondary generalized seizure(SGC).Methods Eleven right handed patients with PS(mean age=18.1±3.6 years,4 males and 7 females) and 11 age,sex,handedness,epileptogenic area and disease duration matched patients with SGC(mean age=19.3±5.6,4 males and 7 females) were recruited.All patients had normal findings on conventional MRI and their diagnoses based on video,EEG telemetry and clinical manifestations. Fifteen right handed age and sex matched normal controls(mean age=18.5±5.5,5 males and 10 females) were also recruited.Diffusion tensor imaging(DTI) was acquired using a 3.0T MR scanner(GE EXCITE,Milwaukee,USA) by employing a spin echo single-shot EPI sequence with 15 directions(TR/TE=10 000/70.8 ms,slice thickness=3.0 mm,FOV=24 cm2,matrix=128×128,b value=0,1 000 s/mm2).Apparent diffusion coefficient(ADC) and FA maps were generated from each participant's DTI scan using DTI-Studio software(http://www.cmrm.med.jhmi.edu).VBA was carried out using SPM2(http://www.fil.ion.ucl.ac.uk/spm/software/).Prior to the analysis,both ADC and FA maps were normalized using the parameters determined from the normalization of the b=0 image to MNI T2 template.All normalized maps were smoothed with a 6-mm FWHM isotropic Gaussian kernel.Statistical comparisons were performed using ANCOVA among PS,SGC and normal controls.A P value of less than 0.05 corrected after multiple comparisons was deemed to be significant.Based on VBA findings,the ROI analysis of bilateral thalami were performed among the three groups using two sample t test in SPSS 11.5 and a P value of less than 0.05 was deemed to be significant.Results VBA analysis showed significantly increased ADC in both PS and SGC groups including bilateral superiorlongitudinal fasciculus,corpus callosum and bilateral temporal stem areas(P corrected<0.05).Only patients with SGC showed significantly increased ADC in bilateral thalami(P corrected<0.05).ROI analysis also showed significantly increased ADC in bilateral thalami in SGC group in comparison with either normal controls or PS group(P<0.05).Conclusion We have observed widely increased ADC and decreased FA in both PS and SGC groups.However,patients with SGC showed significant increased ADC in bilateral thalami than either normal controls or PS,agreeing with the notion that neuronal loss takes place in these areas.This result supports the thalamo-cortical hypothesis that the abnormal function of thalamus cause secondary activation of widespread regions of the brain in patients with generalized seizure.The imaging evidences obtained here provide a further insight into the pathophysiological evolution of SGC and may also be useful for monitoring the therapeutic interventions.