Multimode Functional Magnetic Resonance Imaging Could Predict Response Of Newly Diagnosed Epileptic Patients To Antiepileptic

ObjectiveIn this prospective observational cohort study, we used multimode functionalmagnetic resonance imaging to search the biomarkers which could predictresponse of newly diagnosed epileptic patients to antiepileptic drugs beforedrug taking.MethodsIn this study, the MRI data of newly diagnosed epileptic patients, healthycontrols, drug-resistant epileptic patients, and drug withdrawal patients wereacquired by using G.E.3.0-Tesla scanner. Functional images data werecollected by using an echo-planar imaging sequence. Three dimensionalT1-weighted images data were collected magnetization-prepared rapidgradient echo imaging. Fractional anisotropy (FA) values were derived fromdiffusion tensor imaging (DTI). Different brain regions with low-frequencyfluctuations of spontaneous brain activity in newly diagnosed epilepticpatients with different response to antiepileptic drugs were examined by themean fractional low-frequency fluctuations (mfALFF) using resting-state functional MRI Then the different brain regions were chose for the region ofinterests (ROIs) to built functional connectivity maps to evaluate thedifferences of functional networks in different patients with differentresponse to drugs. Additionally, DTI technology was used to detect thedifferences of white fiber microstructures among different subjects.Results21newly diagnosed epileptic patients,13healthy controls,8drug-resistantepileptic patients and11drug withdrawal patients were recruited into thisstudy. The results showed that:1.mfALFF analysis: there were widespread mfALFF differences amongseizure uncontrolled (SUC) group, seizure controlled (SC) group, andhealthy controls throughout the bilateral cuneus lobe, bilateral lingual gyrus,right middle occipital gyrus, and right inferior frontal gyrus. The SUCpatients showed increased activity mainly in middle occipital gyrus,especially in the cuneus and lingual gyrus, while there was decreasedactivity in the middle frontal gyrus, the inferior frontal gyrus and the inferiorparietal lobule compared with the SC group and healthy controls. Wedemonstrated that the Brodmann17area showed the most significant groupdifferences in mfALFF, and the amplitude low-frequency fluctuations(ALFF) values in the region exhibited a general pattern of ALFF healthycontrols <ALFF patients <ALFF SUC patients. Moreover, by using themfALFF for the Brodmann17area as an index, SUC patients can be differentiated from the SC patients and the healthy controls with highspecificity and sensitivity.2.Functional connectivity analysis: the "default mode" was existed in allhealthy controls and patients. This mode mainly included the posteriorcingulated cortex, medial prefrontal cortex, inferior parietal lobule andinferior temporal gyrus. Compared with the healthy controls and the SCpatients, the SUC patients showed significant increased positive functionalconnectivity with the Brodmann17area in the left posterior central gyrusand the bilateral superior parietal lobule, while increased negative functionalconnectivity with the Brodmann17area in the bilateral posterior cingulatedcortex, bilateral inferior precuneus, medial prefrontal cortex, superior frontalgyrus, and middle frontal gyrus. Compared with the healthy controls, therewas only occipitotemporal junction region that showed decreased positiveconnectivity with Brodmann17area in SC patients. We also found that therewere more brain regions with abnormal functional connectivity in SUCpatients than in SC patients.3. DTI analysis: Compared with the healthy controls, the SUC patientsshowed significantly decreased fractional anisotropy values in the whitefibers under bilateral frontal cortex and the junction cortex of frontal andparietal. There was decreased fractional anisotropy value in the white fibersabove middle cingulated cortex and increased fractional anisotropy value inthe corpus callosum in the SC patients. ConclusionWe find that the abnormal high level of spontaneous brain activity in theoccipital visual cortex region, in particular, the Bromann17area,significantly correlates with the poor response to antiepileptic drugs innewly diagnosed epileptic patients. The abnormal connectivity amongBrodmann17area and superior parietal lobules and the damage of whitefiber microstructures under the frontal and the junction of frontal-parietalcortex may be involved in the formation of antiepileptic drug-resistantnetworks.