What is the initial workup for a patient with suspected Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)?

Workup for Suspected CIDP

The diagnostic workup for suspected CIDP requires electrodiagnostic studies (nerve conduction studies and EMG) as the mandatory cornerstone, combined with MRI spine with and without contrast, CSF analysis, and comprehensive serum testing to exclude mimickers. 1

Essential Clinical Criteria

• Confirm symptom duration of at least 8 weeks to distinguish CIDP from Guillain-Barré syndrome, as this temporal criterion is the primary differentiator 1
• Document the pattern of weakness: typical CIDP presents with symmetric proximal and distal weakness affecting both upper and lower limbs, though variant presentations exist 2
• Look specifically for motor-dominant manifestations with areflexia or hyporeflexia 2

Variant Presentations to Recognize

Be aware that CIDP can present atypically in up to 40% of cases, including: 3

• Pure motor syndrome (10% of cases)
• Sensory ataxic variant (12%)
• Mononeuritis multiplex pattern (9%) - this is the MADSAM variant with multifocal demyelination 2
• Paraparetic pattern (4%)
• Relapsing acute Guillain-Barré syndrome (16%)
• Pain is present in 42% of patients, more common than historically recognized 3

Mandatory Electrodiagnostic Studies

Nerve conduction studies and EMG are non-negotiable for diagnosis 1

• Conduction block is the most common finding, detected in at least one nerve in 73% of patients 3
• F-wave abnormalities occur in 88% of cases 4
• Only 31% have pure demyelinating neuropathy; the majority show some degree of axonal change 3
• These studies must demonstrate peripheral nerve demyelination to confirm diagnosis 2

Critical Imaging

MRI of the entire spine with and without contrast is essential 1

• Evaluate for nerve root enhancement and thickening, which supports the diagnosis 1
• Rule out compressive lesions that can mimic CIDP 5
• Rule out neoplastic causes, particularly important given that 47% of motor CIDP patients have associated inflammatory, infectious, or neoplastic conditions 4
• Use thin axial cuts for optimal visualization 6

CSF Analysis

Perform lumbar puncture with the following studies: 1

• Cell count with differential
• Protein (typically elevated >45 mg/dL in CIDP) 1
• Glucose
• Cytology (mandatory in cancer patients to exclude leptomeningeal disease) 5
• Gram stain 1

Note: Elevated CSF protein with normal or mildly elevated white blood cells is the classic finding, though elevated WBCs can occur in immune checkpoint inhibitor-related cases 5

Comprehensive Serum Testing

Screen for reversible causes and CIDP mimickers: 1

• Diabetes screening (hemoglobin A1c, fasting glucose)
• Vitamin B12 and folate levels
• Thyroid function (TSH)
• HIV testing
• Serum protein electrophoresis with immunofixation (to detect monoclonal gammopathy)
• Consider vasculitic and autoimmune screening panel 5

Critical pitfall: Amyloid neuropathy can perfectly mimic CIDP clinically, electrophysiologically, and on CSF analysis 7. If patients fail to respond to immunomodulatory treatment, strongly consider nerve biopsy to exclude amyloidosis, particularly if autonomic symptoms are present 7

When to Consider Nerve Biopsy

Nerve biopsy is not routinely required if clinical, electrodiagnostic, and CSF findings are consistent with CIDP 1

However, obtain nerve biopsy when: 7

• Patients fail to respond to standard immunomodulatory treatment
• Autonomic involvement is prominent (suggests possible amyloidosis)
• Diagnosis remains uncertain despite complete workup
• Biopsy confirms demyelination with onion bulb formation and inflammatory infiltrates in true CIDP 1

Additional Testing for Specific Scenarios

If acute-onset presentation (maximum severity within 4-8 weeks): 8

• Serum antiganglioside antibody tests for Guillain-Barré syndrome subtypes 5
• Consider diagnosis of acute-onset CIDP if ≥3 relapses occur or progression continues ≥8 weeks after onset 1

If associated with immune checkpoint inhibitor therapy: 5

• Troponin to evaluate myocardial involvement
• ECG and echocardiogram if respiratory insufficiency or elevated CPK
• Consider paraneoplastic autoantibody testing 5

Neurology Consultation

Obtain neurology consultation early in the workup, particularly for grade 2 or higher symptoms 5. Neurologists should guide electrodiagnostic interpretation and help differentiate CIDP from mimickers like amyloidosis, vasculitic neuropathy, or paraneoplastic syndromes.

Common Diagnostic Pitfalls

• Do not assume symmetric presentation: Up to 9% present with mononeuritis multiplex pattern (MADSAM variant) 3
• Do not overlook pain: Present in 42% of cases, contrary to older teaching 3
• Do not miss monoclonal gammopathy: Check serum protein electrophoresis in all patients, as CIDP-MGUS patients have distinct features (greater imbalance, leg ataxia, more sensory loss) but respond equally well to treatment 3
• Do not delay workup for treatment-refractory cases: If no response to immunotherapy occurs, aggressively pursue alternative diagnoses, particularly amyloidosis 7