Peripheral Neuropathy: A Phenotype-Driven Review for Diagnosis and Management.

The purpose of this narrative review is to provide a clinic-ready synthesis of contemporary concepts in peripheral neuropathy, spanning epidemiology, diagnosis, and treatment, with emphasis on high-yield advances applicable to daily practice. The authors integrate pragmatic tools-including a diagnostic algorithm, suggested initial laboratory panels, and commonly used outcome measures-to support clinical decision-making. However, this review is intended as a clinic-oriented synthesis rather than a formal practice guideline. Peripheral neuropathy can be systematically categorized into seven pathophysiologic phenotypes-(1) distal "dying-back" axonopathy, (2) neuronopathy (ganglionopathy), (3) demyelinating neuropathies, (4) small-fiber neuropathy, (5) autonomic neuropathy, (6) ischemic/infiltrative/inflammatory axonopathies, and (7) focal compressive/entrapment neuropathies. An organized evaluation and management around this phenotype-first structure, combined with a structured stepwise escalation algorithm (from bedside pattern recognition to targeted laboratory testing, electrodiagnostics, selective imaging, small-fiber assessment, and immune work-up when indicated), bridges fragmented evidence into a clinic-ready decision-support framework that improves diagnostic precision, rational test utilization, and therapeutic alignment. Beyond optimizing pharmacologic care, neuromodulation may expand options in carefully selected patients. For painful diabetic peripheral neuropathy (DPN), high‑frequency (10 kHz) spinal cord stimulation (SCS) has been evaluated in randomized comparative studies against optimized medical management and has been associated with sustained pain reduction and functional improvement through 24 months in follow‑up reports, supporting consideration in medication‑refractory cases where access and patient factors permit. Ultrasound ‑guided pulsed radiofrequency (PRF)-a nondestructive, field‑based neuromodulation that limits tip temperature to <42 °C-has been studied in small randomized trials and observational cohorts for focal entrapment‑type neuropathic pain after positive diagnostic blocks; reported benefits are generally short‑ to mid‑term with heterogeneous protocols, so certainty varies by indication. For hereditary transthyretin amyloid polyneuropathy (ATTRv), disease‑modifying approaches-including nucleic acid-based therapies-are increasingly integrated into contemporary care. Overall, these developments support earlier pattern recognition, more precise phenotyping, and rational escalation while using standardized outcome measures to track response.