What are demyelinating polyneuropathies, such as Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), in an older adult with a history of diabetes and suspected length-dependent neuropathy?

Demyelinating Polyneuropathies

Demyelinating polyneuropathies are peripheral nerve disorders characterized by damage to the myelin sheath surrounding nerve fibers, distinguished from axonal neuropathies by specific electrodiagnostic patterns showing slowed nerve conduction velocities and prolonged distal latencies. 1, 2

Key Distinguishing Features

Demyelinating vs. Axonal Patterns:

• Demyelinating neuropathies show slowed nerve conduction velocities, prolonged distal latencies, temporal dispersion, and conduction blocks on electrodiagnostic studies 3
• In contrast, axonal neuropathies demonstrate reduced amplitudes with relatively preserved conduction velocities 3
• Nerve biopsy in demyelinating conditions reveals loss of myelin with relative preservation of axons, though this is rarely needed for diagnosis 4

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Clinical Presentation:

• CIDP progresses over more than 2 months, distinguishing it from acute Guillain-Barré syndrome which evolves over days to weeks 1
• Progressive weakness typically starts in the legs and may spread to arms and cranial muscles, with distal paresthesias or sensory loss progressing proximally 5
• Both proximal and distal regions are affected, unlike length-dependent diabetic neuropathy which follows a "stocking-and-glove" distribution 5

Diagnostic Workup:

• Cerebrospinal fluid analysis typically shows cytoalbuminologic dissociation (elevated protein with normal cell count) 1
• Electrophysiological studies demonstrate demyelination patterns and help distinguish CIDP from other neuropathies 1
• MRI of brachial or lumbosacral plexus can identify focal or diffuse peripheral nerve abnormalities 1
• Nerve biopsy may be useful in atypical presentations 1

CIDP in Diabetic Patients: A Critical Diagnostic Challenge

Increased Association:

• CIDP occurs approximately twice as frequently in diabetic patients compared to the general population (relative risk 2.09-2.68) 6
• Among patients with definite or probable CIDP, 18-19.5% have concurrent diabetes 6
• This association is clinically important because CIDP is treatable with immunotherapy, unlike typical diabetic neuropathy 7

Distinguishing CIDP from Diabetic Neuropathy:

• Pattern of involvement: CIDP affects both proximal and distal muscles symmetrically, while diabetic neuropathy is length-dependent and purely distal 5
• Reflexes: CIDP causes diffuse areflexia including proximal reflexes; diabetic neuropathy initially affects only ankle reflexes 4, 2
• Motor involvement: Significant proximal weakness suggests CIDP rather than diabetic neuropathy 1
• Electrodiagnostic findings: Demyelinating features (slowed conduction velocities, prolonged distal latencies, conduction blocks) indicate CIDP; diabetic neuropathy shows axonal loss with reduced amplitudes 3
• CSF protein: Elevated protein without pleocytosis supports CIDP diagnosis 1

Clinical Pitfall:

• Diabetic patients with CIDP show more severe axonal loss on nerve conduction studies and nerve biopsy due to superimposed diabetic axonal polyneuropathy 8
• This overlap can obscure the demyelinating features, making diagnosis more challenging 8, 9
• Despite this, diabetic patients with CIDP respond to immunotherapy with 70% response rates, similar to non-diabetic CIDP patients 6

CIDP Variants

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

• Characterized by asymmetric involvement with preserved reflexes in unaffected areas 1
• Presents with multifocal sensorimotor deficits rather than symmetric patterns 5

Treatment Approach for CIDP

First-Line Therapy:

• For severe or progressing symptoms: pulse methylprednisolone 1g IV daily for 3-5 days plus IVIG 2g/kg over 5 days 1
• IVIG alone (0.4 g/kg for 5 days) is equally effective as plasma exchange 4

Second-Line Options:

• Plasmapheresis for severe cases not responding to initial therapy 1
• Rituximab may be considered in consultation for cases with limited improvement 1

Treatment Response in Diabetic Patients:

• Response rates are similar between diabetic and non-diabetic CIDP patients (70% vs 74.9%) 6
• However, magnitude of functional recovery may be less in diabetic patients due to underlying axonal damage 8
• Long-term follow-up shows sustained improvement with maintenance IVIG therapy 7

Critical Clinical Approach in Older Diabetic Patients

When to Suspect CIDP Rather Than Diabetic Neuropathy:

1. Proximal muscle weakness or proximal reflex loss 1, 5
2. Rapid progression over weeks to months rather than years 1
3. Prominent motor involvement disproportionate to sensory symptoms 3
4. Asymmetric presentation 5
5. Loss of reflexes beyond ankle jerks early in disease course 2

Essential Testing:

• Nerve conduction studies showing demyelinating features are mandatory 1, 3
• CSF analysis for protein elevation without pleocytosis 1
• Consider MRI of nerve roots if diagnosis remains uncertain 1

Common Pitfall to Avoid:

• Do not attribute all neuropathy symptoms to diabetes in patients with known diabetes mellitus—actively screen for treatable demyelinating neuropathies 7, 9
• The presence of diabetes does not exclude CIDP; in fact, it increases the likelihood 6
• Failure to diagnose CIDP in diabetic patients denies them effective immunotherapy 7