Peripheral Neuropathy

Peripheral neuropathy pathophysiology involves distinct mechanisms depending on the etiology. In diabetic neuropathy, hyperglycemia drives injury through four interconnected pathways: (1) the polyol pathway (glucose → sorbitol via aldose reductase, causing osmotic nerve swelling), (2) advanced glycation end-products (AGEs modifying structural proteins and activating RAGE receptors triggering inflammatory cascades), (3) protein kinase C activation (altering vascular permeability and blood flow to vasa nervorum), and (4) hexosamine pathway flux (O-GlcNAcylation of transcription factors altering gene expression). In toxic neuropathies, chemotherapy agents damage the dorsal root ganglion neurons (platinum agents bind DNA; taxanes disrupt microtubule-mediated axonal transport). In immune-mediated neuropathies (GBS, CIDP), molecular mimicry triggers complement-mediated destruction of myelin or axonal gangliosides.