Clinical meaning
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.
Diagnosis & workup
Diagnostics & workup: - Nerve conduction studies to characterize pattern and severity - Quantitative sensory testing (QST) for threshold measurements - Autonomic reflex screen (QSART, heart rate variability, tilt table) for autonomic neuropathy - Nerve biopsy: epineurial vasculitis, amyloid deposits, inflammatory infiltrates, fiber loss quantification - Skin punch biopsy: intraepidermal nerve fiber density (IENFD) for small fiber neuropathy - Serum and urine immunofixation electrophoresis (paraprotein-associated neuropathy) - Genetic testing for hereditary neuropathies (PMP22 duplication for CMT1A)