Are Electromyography (EMG) and Nerve Conduction Velocity (NCV) results the same for Charcot-Marie-Tooth disease type 1 (CMT1) and Charcot-Marie-Tooth disease type 2 (CMT2)?

EMG and NCV Results Differ Significantly Between CMT1 and CMT2

No, EMG and nerve conduction velocity (NCV) results are NOT the same for CMT1 and CMT2—these electrodiagnostic studies are the primary method for distinguishing between these two subtypes and should always be performed for proper classification. 1, 2

Key Electrodiagnostic Differences

Motor Nerve Conduction Velocity (MNCV)

• CMT1 (demyelinating): Median nerve MNCV is always less than 38 m/s, reflecting the underlying demyelinating pathology with damage to the myelin sheath 1, 3
• CMT2 (axonal): MNCV is normal or near-normal (above 38 m/s), though 16% of CMT2 patients may show velocities below 38 m/s, creating some overlap 3, 4
• The slowed conduction velocities in CMT1 are uniform across nerve segments, whereas CMT2 maintains relatively preserved conduction velocities 1, 5

Amplitude Findings

• Both CMT1 and CMT2 show reduced or unobtainable compound muscle action potential (CMAP) and sensory nerve action potential (SNAP) amplitudes in the legs, reflecting length-dependent dysfunction 3
• CMT2 (axonal): Characterized by reduced amplitude with relatively preserved conduction velocities—this is the hallmark finding 1, 2
• CMT1: The reduction in CMAP and SNAP amplitudes results from a combined effect of demyelination and secondary axonal dysfunction 3

Sensory Nerve Conduction Studies

• Sensory nerve conduction velocities (SNCV) show less overlap between CMT1 and CMT2 compared to motor studies 3
• CMT1: SNAP amplitude is more severely reduced and SNAP duration is more prolonged compared to CMT2 3
• SNAP and SNCV evaluation is particularly helpful when motor NCV values overlap, guiding molecular genetic analysis 3

Clinical Correlation

While electrodiagnostic studies clearly differentiate the subtypes, clinical examination alone cannot reliably distinguish CMT1 from CMT2:

• Total areflexia is present in approximately 50% of CMT1 patients but is rare in CMT2 3
• Foot deformities and weakness of knee extensors and foot dorsiflexors are more frequent in CMT1 3
• Age of onset is significantly later in CMT2 compared to CMT1 3
• Most patients in both groups present with the classical CMT phenotype of distal weakness, sensory loss, and foot deformities, making clinical differentiation unreliable 3, 1

Diagnostic Algorithm

Step 1: Perform electrodiagnostic studies on all suspected CMT patients—this is essential and non-negotiable 1, 2

Step 2: Measure median nerve MNCV:

• If MNCV <38 m/s → CMT1 (demyelinating) 1, 4
• If MNCV >38 m/s → CMT2 (axonal) 1, 4
• If MNCV 25-45 m/s → Consider intermediate CMT (CMTX or other subtypes) 4

Step 3: Evaluate CMAP and SNAP amplitudes:

• Reduced amplitudes with slow velocities → CMT1 3
• Reduced amplitudes with preserved velocities → CMT2 1, 3

Step 4: When distal CMAP amplitudes are reduced, evaluate proximal nerve trunks for accurate assessment of conduction slowing 4

Step 5: Use electrodiagnostic classification to guide genetic testing:

• CMT1 → Test for PMP22 duplication (CMT1A) first 1, 2
• CMT2 → Test for MFN2 mutations first 1, 2
• Intermediate velocities → Consider GJB1 (Cx32) mutations for CMTX 1, 2

Critical Pitfalls to Avoid

• Never skip electrodiagnostic studies—they are essential for proper classification and cannot be replaced by clinical examination alone 1, 2
• Do not rely on clinical features alone to differentiate CMT1 from CMT2, as there are no robust clinical signs that reliably distinguish between them 3
• Recognize the 16% overlap where CMT2 patients may have MNCV <38 m/s; use SNAP and SNCV evaluation to clarify these cases 3
• Evaluate proximal nerve segments when distal CMAP amplitudes are attenuated to accurately define the degree of conduction slowing 4
• Remember that both types show length-dependent axonal dysfunction in the legs, so focus on the pattern of velocity slowing versus amplitude reduction 3