PAI-1 4G/5G mutation leads to acute mountain sickness with reversible splenial lesion syndrome and intracranial arteriovenous thrombosis: A case report and literature review

Abstract

Acute mountain sickness (AMS) rarely manifests with concurrent reversible splenial lesion syndrome (RESLES), cerebral venous sinus thrombosis (CVST), and bilateral watershed infarctions. We present the first reported case linking these neurological complications to a plasminogen activator inhibitor-1 (PAI-1) 4G/5G promoter mutation under hypoxic stress. A 23-year-old male developed AMS with encephalopathy and lower limbs weakness following rapid ascent to 3,000m. Critical findings included: 1) Corpus callosum splenium lesions showing RESLES-specific magnetic resonance imaging (MRI) evolution; 2) CVST involving straight and transverse sinuses on magnetic resonance venography (MRV); 3) Watershed infarcts at arterial borderzones. Thrombophilia screening revealed a heterozygous PAI-1 4G/5G mutation, with elevated hematocrit (50.3%) and D-dimer (4.14 μg/mL). Combined anticoagulation (low-molecular-weight heparin transitioning to dabigatran) and hyperbaric oxygen achieved partial venous recanalization at 1-month follow-up, with complete RESLES resolution. In conclusion, this case highlights the complex interplay between genetic factors (PAI-1 mutation), high-altitude hypoxia, and the development of rare cerebrovascular complications, providing valuable insights for clinical diagnosis and treatment.