What is the recommended diagnostic workup and treatment strategy for an adult with suspected chronic inflammatory demyelinating polyneuropathy presenting with progressive symmetric weakness over at least eight weeks?

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

For an adult with suspected CIDP presenting with progressive symmetric weakness over at least eight weeks, initiate first-line treatment with IVIG 2 g/kg over 5 days (0.4 g/kg/day) after confirming demyelinating features on nerve conduction studies and excluding alternative diagnoses. 1

Diagnostic Workup

Clinical Criteria for Diagnosis

• Progressive bilateral weakness with areflexia developing over more than 8 weeks is the hallmark presentation that distinguishes CIDP from acute inflammatory demyelinating polyneuropathy (Guillain-Barré syndrome). 1, 2

• Typical CIDP presents with symmetric proximal and distal weakness affecting both arms and legs, large-fiber sensory loss (vibration and proprioception), and absent or reduced reflexes. 3, 4

• Progression beyond 2 months from symptom onset is the key temporal criterion that separates CIDP from the Guillain-Barré spectrum. 1

Essential Electrodiagnostic Testing

• Nerve conduction studies demonstrating demyelinating features are mandatory for diagnosis—look for reduced conduction velocities, prolonged distal motor latencies, temporal dispersion, conduction blocks, and prolonged or absent F-waves affecting multiple nerves in a relatively uniform pattern. 1, 5

• The demyelinating pattern must be present in multiple nerves bilaterally to distinguish CIDP from focal compressive neuropathies or multifocal motor neuropathy. 6, 3

Cerebrospinal Fluid Analysis

• Obtain CSF to document cytoalbuminologic dissociation (elevated protein with normal cell count <10 cells/μL), which supports the diagnosis but is not specific for CIDP. 1, 4

• Marked CSF pleocytosis should prompt reconsideration of the diagnosis and evaluation for alternative causes such as infection or malignancy. 2

Exclusion of Mimics (Critical Step)

• Perform serum protein immunofixation electrophoresis to exclude monoclonal gammopathy-associated neuropathies, which can present identically to CIDP but require different treatment. 1, 4

• Order metastatic bone survey or skeletal imaging to rule out osteosclerotic myeloma (POEMS syndrome). 4

• Check HIV serology, as HIV-associated neuropathy can mimic CIDP. 4

• Obtain fasting glucose/HbA1c, vitamin B12 with metabolites, and TSH to exclude common metabolic causes of demyelinating neuropathy. 5

Neuroimaging

• MRI of the spine with contrast is required when focal neurological signs, gait disturbance with upper motor neuron features, or increased reflexes are present to exclude CNS involvement or compressive lesions. 1, 5

• MRI may demonstrate nerve root enhancement or thickening in CIDP, supporting the diagnosis. 5

First-Line Treatment Strategy

Immediate Treatment Initiation

• Begin IVIG 2 g/kg administered over 5 days (0.4 g/kg/day) as the preferred first-line therapy for typical CIDP. 1

• IVIG achieves 60-75% response rates and is preferred over corticosteroids due to better tolerability and fewer long-term side effects. 1

Alternative First-Line Options

• For severe or rapidly progressive disease, consider pulse methylprednisolone 1 g IV daily for 3-5 days followed by oral prednisone taper over 4-6 weeks. 1

• Plasma exchange (200-250 mL/kg over 4-5 sessions) is equally effective as IVIG and should be considered when IVIG is contraindicated or unavailable. 1, 2

• Critical timing consideration: Do not perform plasmapheresis immediately after IVIG administration, as it will remove the therapeutic immunoglobulin. 1

Treatment Response Monitoring

• Approximately 40% of patients do not show improvement in the first 4 weeks—this does not necessarily indicate treatment failure, as progression may have been worse without therapy. 1, 2

• Assess response using objective measures: improvement in muscle strength (Medical Research Council scale), functional disability scores, or repeat nerve conduction studies showing improved conduction velocities or amplitudes. 4

• Treatment-related fluctuations (TRFs) occur in 6-10% of patients, defined as disease progression within 2 months after initial treatment-induced improvement. 1

• For TRFs, repeat the full course of IVIG or plasma exchange, as this indicates the treatment effect has worn off while inflammation persists. 1

Management of Refractory or Inadequate Response

Second-Line Immunosuppression

• When symptoms do not resolve after 4 weeks of first-line therapy or when corticosteroid-sparing is needed, add methotrexate, azathioprine, or mycophenolate mofetil. 1

• Rituximab should be considered in consultation with neurology for patients with limited or no improvement after first-line therapy, particularly in antibody-mediated CIDP variants. 1, 6

Maintenance Therapy

• Patients who respond to initial IVIG typically require ongoing maintenance therapy every 3-4 weeks to prevent relapse. 7, 8

• Subcutaneous immunoglobulin is now approved as an alternative maintenance option that may improve patient independence and tolerability. 7, 3

Common Diagnostic and Treatment Pitfalls

Timing Errors

• Do not delay treatment beyond 2 weeks once CIDP is suspected, as this is associated with severe neurological deficit and poor outcomes. 1

• Do not dismiss CIDP if nerve conduction studies are normal in the first week—repeat testing in 2-3 weeks if clinical suspicion remains high. 1, 2

Misdiagnosis Risks

• Bilateral simultaneous weakness progressing over weeks to months should immediately raise suspicion for CIDP rather than multiple focal compressive neuropathies. 2

• Asymmetric presentations, predominant motor involvement without sensory loss, or conduction block limited to common entrapment sites suggest alternative diagnoses such as multifocal motor neuropathy or Lewis-Sumner syndrome (multifocal CIDP variant). 6, 3

Treatment Sequencing Errors

• Do not use sequential plasma exchange followed by IVIG (or vice versa), as this approach has not shown benefit and wastes the first treatment. 2

• Corticosteroids alone are not recommended as monotherapy for typical CIDP when IVIG or plasma exchange are available. 2

Special Considerations for CIDP Variants

• Multifocal acquired demyelinating sensory and motor neuropathy (Lewis-Sumner syndrome) presents with asymmetric, multifocal deficits and may respond differently to treatment than typical CIDP. 6, 3

• Distal acquired demyelinating symmetric neuropathy (DADS) affects only distal limbs and may be associated with IgM paraproteinemia, requiring different management. 6, 3

• Patients with antibodies against nodal proteins (neurofascin, contactin-1) often show refractory response to IVIG and may require alternative immunosuppression earlier. 6, 3

Prognosis and Long-Term Monitoring

• With appropriate treatment, most CIDP patients achieve functional improvement, though complete recovery is less common than in Guillain-Barré syndrome. 8, 4

• Serial neurologic examinations are preferred over repeated nerve conduction studies for monitoring stable, treated CIDP. 5

• Repeat electrodiagnostic testing is only warranted when there is clinical uncertainty about new or worsening neurological processes. 5