To describe a case of copper deficiency myelopathy presenting as progressive spastic quadriparesis and malnutrition following substantial weight loss associated with tirzepatide (Mounjaro) use.

Copper deficiency myelopathy (CDM) is an uncommon, potentially reversible condition that presents with subacute combined degeneration-like symptoms. It is classically associated with prior gastric surgery, malabsorption, or zinc excess, but may also arise from severe nutritional deficiency. As GLP-1/GIP receptor agonists gain popularity for weight management, emerging reports describe neurological sequelae related to rapid or excessive weight loss and ensuing micronutrient deficiencies. We present a case of CDM in a patient with no surgical history, suggesting a novel association with tirzepatide-induced malnutrition.

A 40-year-old woman with obesity and type 2 diabetes developed progressive numbness, gait instability, and lower extremity spasticity after >80-lb weight loss during tirzepatide therapy. Examination revealed spastic quadriparesis, proprioceptive loss, and sustained clonus. Routine metabolic, autoimmune, and infectious studies were unrevealing; vitamin B12 and folate were normal. MRI of the cervical and thoracic cord demonstrated central T2 hyperintensity consistent with a subacute combined degeneration pattern. Serum copper was low (66 µg/dL), confirming copper deficiency myelopathy in the setting of marked malnutrition. She was treated with intravenous followed by oral copper repletion, leading to stabilization and modest neurological improvement, though residual spastic paraparesis persisted at follow-up.

This case expands the spectrum of neurologic complications associated with GLP-1/GIP agonist therapy. Rapid pharmacologic weight loss may precipitate trace element deficiencies—including copper, thiamine, and zinc—that contribute to neuropathy or myelopathy. Although GLP-1 analogues have demonstrated neuroprotective effects in preclinical models, their gastrointestinal effects can impair nutrient absorption and promote deficiency states. Clinicians should maintain vigilance for micronutrient-related neurological syndromes in patients on GLP-1–based therapy who develop subacute motor or sensory deficits. Early identification and supplementation are essential to halt progression and optimize recovery.