This work represents one attempt to develop a computer aided diagnosis system for epilepsy lesion detection based on neuroimaging data, in particular T1-weighted and FLAIR MR sequences. Given the complexity of the task and the lack of a representative voxel-level labeled data set, the adopted approach, first introduced in Azami et al., 2016, consists in casting the lesion detection task as a per-voxel outlier detection problem. The system is based on training a one-class SVM model for each voxel in the brain on a set of healthy controls, so as to model the normality of the voxel. The main focus of this work is to design representation learning mechanisms, capturing the most discriminant information from multimodality imaging. Manual features, designed to mimic the characteristics of certain epilepsy lesions, such as focal cortical dysplasia (FCD), on neuroimaging data, are tailored to individual pathologies and cannot discriminate a large range of epilepsy lesions. Such features reflect the known characteristics of lesion appearance; however, they might not be the most optimal ones for the task at hand. Our first contribution consists in proposing various unsupervised neural architectures as potential feature extracting mechanisms and, eventually, introducing a novel configuration of siamese networks, to be plugged into the outlier detection context. The proposed system, evaluated on a set of T1-weighted MRIs of epilepsy patients, showed a promising performance but a room for improvement as well. To this end, we considered extending the CAD system so as to accommodate multimodality data which offers complementary information on the problem at hand. Our second contribution, therefore, consists in proposing strategies to combine representations of different imaging modalities into a single framework for anomaly detection. The extended system showed a significant improvement on the task of epilepsy lesion detection on T1-weighted and FLAIR MR images. Our last contribution focuses on the integration of PET data into the system. Given the small number of available PET images, we make an attempt to synthesize PET data from the corresponding MRI acquisitions. Eventually we show an improved performance of the system when trained on the mixture of synthesized and real images.