Polyneuropathy, axonal and demyelinating neuropathies (mechanism of disease)

This is a flowchart on polyneuropathy, covering axonal neuropathy and demyelinating neuropathy, including the etiology, pathophysiology, and manifestations of these conditions.

ADDITIONAL TAGS:
Hypothyroidism
Variable progression, with
periods of recovery, stabilization, exacerbations, slow decline, etc.
Progression: slow decline over years, affecting longer axons (lower extremities) first.
Distal muscle wasting: feet, lower legs, hands (if severe)
Damage to multiple peripheral nerve fibers, mainly involving:
Axon loss → ↓ signal
amplitude (axonal neuropathy)
Risk factors / SDOH
Cell / tissue damage
Nutrition / diet
Polyneuropathy
Medicine / iatrogenic
Infectious / microbial
Biochem / metabolic
Immunology / inflammation
Signs / symptoms
Tests / imaging / labs
Environmental / toxin
Genetic / hereditary
Flow physiology
Pathophysiology
Etiology
Manifestations
Alcohol use disorder
Impaired interaction between Schwann cells and axons →
↓ conduction velocity, ↑ latency (demyelinating neuropathy)
Generalized muscle weakness: distal proximal
Distal sensory loss (abnormal vibration and proprioception pain or temperature)
Diffusely ↓ or absent reflexes
Distal sensory loss (all senses: pain, temperature, proprioception, vibration)
↓ or absent distal reflexes (usually begins in the ankles)
Atrophy of muscles
+/- neuropathic pain, paresthesias, and motor weakness
Burning-foot syndrome: burning pain, tingling, pins-and-needles sensation, or formication (feels like insects crawling on/under skin)
Sensory ataxia
Malnutrition (↓ thiamine)
Cytotoxic effects
Alcoholic polyneuropathy
Diabetes mellitus
Chronic hyperglycemia
Glycation of axon proteins
HIV
Leprosy
Borreliosis
Chemotherapy-induced peripheral neuropathy (cisplatin, doxorubicin)
Drug-induced (suramin, amiodarone)
Diphtheria → diphtheria toxin
Charcot-Marie-Tooth disease (aka Hereditary motor sensory neuropathy)
Scoliosis
Foot deformities (high arches, hammer toes)
Krabbe disease, adrenoleukodystrophy, metachromatic leukodystrophy
Other inflammatory: vasculitis; connective tissue disorders
Other viruses: CMV, VZV, herpes zoster, measles, mumps, rubella, flu
Uremic polyneuropathy
Heavy metals (lead, arsenic, thallium)
Guillain-Barré: cross reactive Ab (molecular mimicry against Schwann cells)
GI or resp infxn
Motor sensory in early dz