Resolution of severe lumbar spinal epidural lipomatosis following tirzepatide-induced weight loss: illustrative case.

BACKGROUND: Spinal epidural lipomatosis (SEL) is a rare disorder characterized by pathological accumulation of adipose tissue in the spinal epidural space, leading to signs and symptoms of lumbar stenosis. SEL is increasingly linked to obesity, and treatment requires surgical decompression if conservative measures fail. The role of modern pharmacological weight-loss agents in reversing SEL has not been previously described. OBSERVATIONS: A 35-year-old man with severe, symptomatic lumbar SEL and class II obesity (BMI 37.8 kg/m) presented with progressive neurogenic claudication and functional decline. MRI revealed multilevel lumbar SEL with severe spinal stenosis. After counseling, the patient initiated tirzepatide therapy and achieved approximately 60 pounds of weight loss within 1 year. This was accompanied by marked symptom resolution and near-complete regression of epidural fat on repeat MRI, negating the need for surgical intervention. LESSONS: This case demonstrates that pharmacological weight loss with agents such as tirzepatide may offer a viable, nonoperative alternative for patients with obesity-related SEL, particularly those who are not ideal surgical candidates. Validation in larger studies is needed to assess long-term efficacy and help guide patient selection for pharmacological versus surgical approaches. https://thejns.org/doi/10.3171/CASE25886.