What are the diagnostic criteria for Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)?

CIDP Diagnostic Criteria

The diagnosis of CIDP requires three core elements: (1) a clinical phenotype of typical CIDP or recognized variant, (2) electrophysiological evidence of peripheral nerve demyelination, and (3) exclusion of alternative causes, as established by the European Academy of Neurology/Peripheral Nerve Society 2021 guidelines. 1

Clinical Phenotype

Typical CIDP presents with the following features:

• Symmetric proximal and distal muscle weakness progressing over at least 8 weeks, distinguishing it from acute inflammatory demyelinating polyneuropathy (Guillain-Barré syndrome) 1
• Sensory symptoms including numbness, paresthesias, and proprioceptive loss affecting distal extremities in a length-dependent pattern 2
• Areflexia or hyporeflexia, typically beginning with absent ankle jerks and progressing proximally 3
• Progressive or relapsing-remitting course over months to years 4

CIDP variants include atypical presentations that still represent the disease spectrum:

• Distal CIDP (predominantly distal weakness and sensory loss) affecting 17% of cases 5
• Pure sensory CIDP (exclusively sensory polyneuropathy without motor involvement) in 15% of cases 5
• Asymmetric/multifocal CIDP (markedly asymmetric disease or mononeuritis multiplex pattern) in 8% of cases 5
• Focal CIDP with predominant cranial nerve involvement in 5% of cases 5

Electrophysiological Criteria

Nerve conduction studies must demonstrate demyelinating features in at least one motor nerve or two sensory nerves 5:

Motor Nerve Demyelination Indicators

• Prolonged distal motor latencies exceeding normal limits adjusted for temperature and distal CMAP amplitude 6
• Slowed motor conduction velocities below the minimum expected for the degree of axonal loss 6
• Conduction block (>30% amplitude reduction between proximal and distal stimulation sites without temporal dispersion) 7
• Temporal dispersion with abnormal waveform morphology 7
• Prolonged or absent F-wave latencies indicating proximal demyelination 7
• Multiple A-waves suggesting abnormal nerve excitability in demyelinating conditions, found in 50% of atypical CIDP cases 7

Critical Technical Considerations

• Temperature standardization is essential: nerve conduction studies should be performed with limbs warmed to 37°C for at least 30 minutes, as criteria for demyelination vary significantly with temperature 6
• Amplitude-adjusted criteria: more stringent criteria for distal motor latency and conduction velocity apply when distal CMAP amplitude is below 1 mV, as axonal loss itself causes some slowing 6
• Segment-specific criteria: different thresholds apply for upper arm/shoulder segments versus lower arm/leg segments 6

Sensory Nerve Findings

• Abnormal median-to-sural amplitude ratio (low median relative to sural nerve) suggests demyelinating process in 50% of atypical cases 7
• Prolonged sensory latencies or slowed sensory conduction velocities in at least two nerves 5

Exclusion Criteria

The following conditions must be ruled out before confirming CIDP diagnosis 1:

• Multifocal motor neuropathy (pure motor, conduction block without sensory involvement)
• Anti-MAG neuropathy (IgM paraprotein with anti-MAG antibodies)
• Autoimmune nodopathy (anti-contactin-1, anti-neurofascin antibodies)
• Hereditary neuropathies including CMT1A, HNPP, and other genetic causes 2
• Diabetic polyneuropathy, though diabetes may coexist with CIDP 3
• Toxic/metabolic causes: B12 deficiency, hypothyroidism, uremia, paraproteinemias 3
• Vasculitic neuropathy and other inflammatory conditions 3

Supportive Diagnostic Testing

When Standard Electrodiagnostics Are Atypical

Nerve biopsy is valuable when clinical suspicion is high but electrodiagnostic criteria are not met, demonstrating specific demyelinating features including onion bulb formation, segmental demyelination, and inflammatory infiltrates 7. In one series, 8 of 44 patients (18%) with clinically suspected CIDP required nerve biopsy for diagnostic confirmation when standard criteria were not fulfilled 7.

Additional Laboratory Evaluation

• CSF analysis typically shows albuminocytologic dissociation (elevated protein >45 mg/dL with cell count <10/μL), though this has low diagnostic yield except in suspected demyelinating polyneuropathies 2
• Serum protein immunofixation electrophoresis to exclude paraproteinemic neuropathies 2
• Comprehensive metabolic panel, glucose, B12, TSH to exclude mimics 2

Common Diagnostic Pitfalls

• Applying overly restrictive criteria: The 1991 AAN research criteria miss approximately 54% of CIDP cases that have atypical presentations but respond to immunotherapy 5
• Ignoring temperature effects: Failure to standardize limb temperature to 37°C leads to false interpretation of conduction velocities 6
• Overlooking amplitude-dependent slowing: Not adjusting criteria when distal CMAP is <1 mV reduces specificity 6
• Missing CIDP variants: Exclusively sensory or distal presentations are legitimate CIDP phenotypes requiring recognition 5
• Relying solely on F-waves: While supportive, F-wave abnormalities alone are insufficient without other demyelinating features 7

Clinical Spectrum Recognition

The spectrum of CIDP is broader than traditional criteria suggest, with 54% of electrophysiologically confirmed cases presenting with features outside the classic symmetric proximal-distal weakness pattern 5. Recognition of this broader spectrum is clinically important because these atypical cases frequently respond to immunosuppressive therapy, with 83% (5 of 6 treated patients) showing favorable response in one series 7.