What are the types of demyelinating neuropathies and their treatments?

Types of Demyelinating Neuropathies

Demyelinating neuropathies are classified primarily by their time course: acute forms (Guillain-Barré syndrome and variants) progress over days to 4 weeks, while chronic forms (CIDP and variants) progress beyond 2 months. 1, 2

Acute Demyelinating Neuropathies (Guillain-Barré Syndrome Spectrum)

Acute Inflammatory Demyelinating Polyneuropathy (AIDP)

• Most common GBS subtype in Western countries, characterized by macrophage-mediated demyelination with lymphocytic infiltration 3, 4, 5
• Presents with progressive bilateral ascending weakness affecting limbs initially, potentially progressing to cranial and respiratory muscles 3
• Requires absent or decreased tendon reflexes in affected limbs at some point during clinical course 1
• Progression occurs over days to 4 weeks 1, 2

Acute Motor Axonal Neuropathy (AMAN)

• Pure motor variant more common in outbreaks associated with Campylobacter jejuni infection, particularly in northern China and Mexico 3, 5
• Distinguished from AIDP by predominantly axonal rather than demyelinating features on nerve conduction studies 3

Acute Motor and Sensory Axonal Neuropathy (AMSAN)

• Involves both motor and sensory axonal degeneration 5
• Generally associated with more severe disease course than AIDP 5

Miller Fisher Syndrome (MFS)

• Classic triad: ophthalmoplegia, ataxia, and areflexia 3
• Distinct clinical presentation from typical GBS 3

Acute Pandysautonomia

• Rare variant affecting autonomic nervous system 5

Chronic Demyelinating Neuropathies (CIDP Spectrum)

Classic CIDP

• Progression beyond 2 months is the key distinguishing feature from GBS 1, 2
• Presents with progressive bilateral weakness with areflexia 1
• Cerebrospinal fluid shows cytoalbuminologic dissociation (elevated protein with normal cell count) 1, 2
• Electrophysiological studies demonstrate demyelinating features 1, 2

Multifocal Acquired Demyelinating Sensory and Motor Neuropathy (MADSAM/Lewis-Sumner Syndrome)

• Characterized by asymmetric involvement with preserved reflexes in areas not affected by weakness 2, 5
• Distinct from classic CIDP by multifocal rather than diffuse pattern 5

Distal Acquired Demyelinating Symmetric Neuropathy (DADS)

• Variant with predominantly distal involvement 5
• May be associated with IgM paraproteinemia 5

IgM-Associated Demyelinating Neuropathy (Anti-MAG Neuropathy)

• 50% of patients with IgM MGUS and peripheral neuropathy have anti-myelin-associated glycoprotein (MAG) antibodies 3
• Presents as slowly progressing, symmetrical sensory peripheral neuropathy affecting feet initially 3, 4
• IgM M-protein can also target other neural antigens including GD1b ganglioside, sulphatide, and chondroitin sulphate 3

Treatment Approaches by Type

Acute Demyelinating Neuropathies (GBS)

• Plasma exchange is indicated for severely paralyzed patients or those with rapid deterioration suggesting imminent need for ventilatory support 6
• Corticosteroids are NOT supported by evidence in acute GBS 6
• Urgent hospitalization with respiratory monitoring required 4

Chronic Demyelinating Neuropathies (CIDP)

For severe or progressing symptoms:

• Pulse corticosteroids (methylprednisolone 1g IV daily for 3-5 days) PLUS IVIG 2g/kg over 5 days (0.4 g/kg/day) 3, 2
• Plasmapheresis for cases not responding to other therapies 2, 6
• Taper steroids following acute management over at least 4-6 weeks 3

For maintenance therapy:

• Prednisone is effective but long-term use causes significant adverse effects 7
• IVIG can be used as first-line treatment or for steroid-unresponsive patients 8, 7
• Azathioprine, mycophenolate mofetil, or cyclosporine as steroid-sparing agents 7

For refractory cases:

• Rituximab may be considered in consultation for limited improvement 3, 2, 7
• Cyclophosphamide reserved for progressive, treatment-resistant disease 7

IgM-Associated Neuropathy

• Rituximab is effective in part of patients with IgM neuropathy 3, 7
• Combination of prednisone and cyclophosphamide may improve numbness and strength 7

Critical Diagnostic Algorithm

Step 1: Establish time course 1, 2

• Days to 4 weeks → Consider GBS spectrum
• Beyond 2 months → Consider CIDP spectrum

Step 2: Confirm clinical features 1

• Progressive bilateral weakness with areflexia required for GBS/CIDP
• Assess for red flags suggesting alternative diagnoses

Step 3: Obtain CSF analysis 1

• Look for cytoalbuminologic dissociation (elevated protein, normal cell count)

Step 4: Perform nerve conduction studies 1, 4

• Document demyelinating features: slowed conduction velocity, prolonged distal latencies, conduction block
• Distinguish from axonal neuropathies (preserved velocity with reduced amplitude)

Step 5: Additional workup for CIDP 1

• Serum electrophoresis with immunofixation
• Metastatic bone survey
• HIV testing
• Consider MRI of brachial/lumbosacral plexus 2

Step 6: Consider nerve biopsy only for atypical presentations 1, 2

Common Pitfalls

• Do not confuse IgA/IgG MGUS-associated neuropathy with true demyelinating disease—the association is less clear and MGUS may be incidental 3
• Central demyelination (multiple sclerosis, acute disseminated encephalomyelitis) may worsen with anti-TNF therapy and is a contraindication 3
• Exclude treatable causes before attributing neuropathy to inflammatory demyelination: vitamin deficiencies (B12, D, E, folate, thiamine, copper), hypothyroidism, diabetes, hepatitis C, and medication-induced (especially metronidazole) 3
• Multifocal motor neuropathy with conduction block responds to IVIG but may slowly worsen over time despite treatment 7