Acute ischemic stroke in young adults without traditional vascular risk factors often requires evaluation for uncommon etiologies such as paradoxical embolism. May-Thurner syndrome (MTS), characterized by compression of the left common iliac vein, predisposes to deep vein thrombosis (DVT), while patent foramen ovale (PFO) facilitates right-to-left shunting of thrombi, increasing embolism risk. The combination of MTS and PFO is rare and underrecognized in stroke pathogenesis.

A 33-year-old African-American male with no significant medical history presented with acute aphasia and right-sided weakness following minor trauma. Imaging revealed left middle cerebral artery territory infarcts. Comprehensive diagnostics, including transesophageal echocardiography, identified PFO with right-to-left shunt, and magnetic resonance venography confirmed MTS with left iliac vein compression. Treatment involved prompt mechanical thrombectomy, anticoagulation with apixaban, and planned PFO closure. The patient achieved full neurological recovery with NIH Stroke Scale score of 0 at discharge.

This case highlights the synergistic role of MTS and PFO in paradoxical embolic stroke, underscoring the importance of high clinical suspicion and multimodal imaging in cryptogenic stroke evaluation. Despite the absence of overt thrombosis, multidisciplinary management led to complete recovery, advocating for systematic etiological workup in young adults with atypical presentations.