A patient presenting with acute confusion, dysarthria, and appendicular ataxia with gait instability warrants a broad differential including emergent consideration of acute ischemic or hemorrhagic stroke. Moreover, in acute to subacute presentations, a wide array of etiologies including infectious causes, toxins, or autoimmune conditions may be considered. This article features a 47-year-old man who presented acutely with confusion, severe dysarthria, left upper extremity dysmetria, and unsteady gait. In this case, these neurologic signs were preceded by symptoms of an upper respiratory infection. In addition, MRI brain without contrast demonstrated a small focus of hyperintensity on diffusion-weighted imaging in the splenium of the corpus callosum with apparent diffusion coefficient match. The article illustrates a diagnostic approach in evaluating a patient with this constellation of clinical and radiologic findings, as well as pertinent management considerations. A comprehensive overview of other potential causative factors of the imaging findings is described to augment the reader's differential diagnosis. Finally, a literature review pertaining to the revealed diagnosis highlights the epidemiologic relevance and important clinical pearls.