We used conventional MRI to longitudinally assess lesion pathology in a combined cuprizone and experimental autoimmune encephalomyelitis (CPZ/EAE) model. The novelty of this model lies in the recruitment of cells from the innate and adaptive immune system into brain lesions. We used T2-weighted imaging to monitor white matter lesions. Interestingly, we showed a transient change in T2 contrast at the onset of clinical symptoms in the CPZ/EAE group. Using gadolinium-enhanced MRI, we showed transient opening of the blood-brain-barrier prior and/or following clinical symptoms. Altogether, these findings are of relevance to understand the dynamics of lesion formation in a novel MS model.