Table 2.
Demyelinating polyneuropathy differential diagnosis
| Disease | Comment | Electrophysiology | CSF protein |
|---|---|---|---|
| Immune | |||
| AIDP | Progressive over < 4 weeks | F waves prolonged early; demyelinating features peak 2–3 weeks | Normal or ↑ |
| MAG | Distally accentuated, with slow progression most common | Distally accentuated slowing | ↑ |
| MMN | Multifocal; spared sensation | CB in many | Normal or ↑ |
| POEMS (see Comment column) | Polyneuropathy; Organomegaly; Endocrinopathy; M-protein; Skin changes | ↑ axonal injury and more uniform CV slowing than usually seen in CIDP | ↑ |
| Drug-induced | Tumor necrosis factor-alpha antagonists (infliximab, adalimumab, etanercept); interferon-alpha therapy, tacrolimus, bortezomib, pembrolizumab | May be indistinguishable from CIDP | Normal or ↑ |
| Metabolic | |||
| Diabetic | Usually length-dependent with small fiber involvement; plexopathy may be abrupt onset | Usually axonal; may have mild/moderate demyelination without TD or CB | Normal or ↑ |
| Uremic | Glomerular filtration rate typically < 12 mL/min | Usually axonal; may have mild/moderate demyelination | Normal or ↑ |
| Toxic | |||
| Amiodarone | Subacute/chronic; symmetric sensorimotor; may affect proximal muscles; ↑ risk if exposure > 1 year | Axon loss + mild to moderate CV slowing and prolonged DL | Normal |
| Ethylene glycol | CNS; CN changes; renal and cardiac toxicity | Axon loss predominates | ↑ |
| Diptheria | Usually evolves over 2–3 weeks; ± CSF pleocytosis,;bulbar and respiratory weakness common | May be indistinguishable from CIDP | ↑ |
| n-Hexane | May mimic distal CIDP, with distal > proximal sensory and motor symptoms evolving over months | Usually axonal; may have mild/moderate demyelination or CB | Normal |
| Systemic | |||
| Amyloid, acquired or hTTR | Prominent pain and autonomic dysfunction; cardiac or gastrointestinal manifestations | Typically axonal; mild to moderate CV slowing may be seen | Normal or ↑ |
| Sarcoid | Pulmonary, skin, ocular, muscle, endocrine, CN, or CNS involvement | Typically multifocal axonal or LDPN; rarely demyelinating with CB | Normal or ↑ |
| Malignancy | |||
| Neurolymphomatosis | Often multiple mononeuropathy pattern; pain common; CNs may be affected; may improve with immunotherapy | Usually axonal, but may have multifocal demyelinating features similar to CIDP | Normal or ↑ |
| Paraneoplastic | Asymmetric sensory or sensorimotor often preferentially affecting DRG; concomitant CNS disorder may occur | Sensory responses often diffusely attenuated or absent; motor responses usually normal or show axonal changes, but demyelination mimicking CIDP has been reported | ↑ |
| Inherited | |||
| HNPP | Symptoms triggered by mild trauma or compression | CB accentuated at compressible sites | Normal or ↑ |
| CMT 1 | Slow progression, often with onset at early age | Uniform CV slowing; typically without CB or TD (exceptions may occur) | Normal or ↑ |
| Farber’s | X-linked; onset childhood or adolescence; pain; angiokeratomas; premature atherosclerosis | Slow CV and ↑ DL; may be normal early in disease | Normal or ↑ |
| Refsum | AR; onset usually in infancy or early adult; course may be progressive or relapsing; retinitis pigmentosa, cerebellar ataxia, hearing loss, cardiac conduction disease | Demyelinating with severe CV slowing | ↑ |
| MLD | AR; arylsulfatase A mutation; onset most common in late infancy, followed by adolescence and then as adult; multiple CNS deficits | CV slowing without CB | ↑ |
| Krabbe | AR; galactosylceramide β-galactosidase mutation; onset in infancy, adolescence, adulthood; multiple CNS deficits | Slow CV, occasional with CB | ↑ |
| Mitochondiral | |||
| MNGIE | Onset childhood or adolescence; myopathy; external ophthalmoplegia; neuropathy; gastrointestinal; encephalopathy (may be subclinical) | Demyelinating with CV slowing; CB and TD in some patients | ↑ |
AIDP Acute inflammatory demyelinating polyradiculoneuropathy, AR autosomal recessive, CB conduction block, CN cranial nerve, CNS central nervous system, CV conduction velocity, DRG dorsal root ganglion, CSF cerebrospinal fluid, DRG dorsal root ganglia, DL distal latency, HNPP hereditary neuropathy with pressure palsies, hTTR hereditary transthyretin amyloidosis, LDPN length-dependent polyneuropathy, MAG Anti-myelin-associated glycoprotein, MLD metachromatic leukodystrophy, MMN multifocal motor neuropathy TD temporal dispersion, ↑ increased