To highlight the clinical presentation of an artery of Percheron (AOP) stroke in order to differentiate an acute change in mentation caused by a diffuse process from that caused by a structural lesion.

Bilateral thalamic infarction can result from an AOP, a rare anatomical variant that supplies both paramedian thalami and the rostral mesencephalon. Its presentation of altered consciousness with other variable focal features poses a diagnostic challenge. Here we describe a case of AOP infarction presenting with impaired arousal and disconjugate gaze.

A 53‐year‐old female with hypertension, hyperlipidemia, and type 2 diabetes mellitus was stroke activated for headache, confusion, aphasia, dysarthria, and left sided weakness.  She was immediately intubated for airway protection. Pre-intubation exam showed a right dilated, non-responsive pupil and disconjugate gaze. CT angiogram of the head demonstrated high‐grade stenosis versus occlusion of the right P1 segment. CT perfusion revealed a perfusion defect in the right posterior inferior cerebellar artery (PICA) territory. The patient received intravenous tenecteplase 175 minutes after last known well without complications. Magnetic resonance imaging of the brain showed moderate-sized infarcts in the right PICA and AOP territories, involving the bilateral medial thalami and periaqueductal midbrain. Workup suggested a cardioembolic source due to a left ventricular thrombus. She improved clinically, following simple commands and moving all extremities, though disconjugate gaze persisted.

Diffuse processes such as toxic or metabolic derangements are typically prioritized in the differential diagnosis of patients with altered mental status. However, subtle focal deficits, such as the disconjugate gaze and dilated pupil seen in our patient, can help shift suspicion toward structural causes, like a brainstem or bilateral medial thalamic stroke. This case underscores the need for a high diagnostic suspicion of AOP infarcts despite their rarity and diverse clinical presentation, as early intervention may improve patient outcomes.