The phantom paradox: Protective and risk factors for phantom limb pain following major lower extremity amputation

BackgroundApproximately 50% to 80% of individuals undergoing amputation experience some form of phantom limb syndrome (PLS), a debilitating complication following major amputations that significantly diminishes patient quality of life, particularly PLS with pain (PLP). Yet, comprehensive studies exploring potential risk factors remain scarce. This large retrospective study identified major risk factors for PLP to help guide preoperative risk stratification and perioperative care strategies.MethodsA national healthcare database was utilized to identify adults undergoing major lower extremity amputation (LEA) between 2012 and 2024. Patients were propensity score-matched across 31 demographic, clinical, and surgical variables. 18 distinct exposure cohorts, categorized into demographic, metabolic/vascular, substance use/medication history, and psychosocial/surgical factors, were analyzed to assess their associated risk for PLP within 1-year following LEA.ResultsAcross 18 comparisons (n ≈ 12,000-88,000 per cohort), significant risk factors associated with increased PLP included preoperative limb pain (RR: 1.386), active tobacco use (RR: 1.372), hereditary and idiopathic neuropathy (RR: 1.261), peripheral arterial disease (RR: 1.117), and preoperative infection (RR: 1.160). Factors associated with reduced PLP risk included dementia (RR: 0.470), advanced age ≥65 (RR: 0.697), end-stage renal disease (RR: 0.771), and diabetes mellitus (RR: 0.790).ConclusionsThis study identified preoperative pain, neuropathy, tobacco use, peripheral arterial disease, and infection as risk factors, and dementia, dialysis, older age, diabetes, and above-knee amputation as protective against PLP. These findings support evidence-based preoperative risk stratification, targeted counseling, and optimization of modifiable risk factors. Prospective studies are needed to validate these associations, informing clinical prediction tools and targeted interventions aimed at improving patient outcomes.