NCS Pathology

The main types of pathology affecting nerve conduction studies are 1) axonal and 2) demyelinating. Looking at amplitude and conduction velocity is key to differentiating between axonal vs demyelinating pathology, but these MUST be correlated with EMG findings and the clinical context. 

Differentiating between axonal and demyelinating neuropathy helps narrow the differential diagnosis and guide prognosis.

As always, it is also important to be aware of and eliminate possible artifact that may be confounding results.

Axonal pathology

Axonal lesions typically result in decreased amplitude with relatively preserved conduction. However,  axonal loss can affect conduction especially if it is severe, and conversely severe demyelination can affect amplitude. Thus, DO NOT assume that decreased CMAP and SNAP reduction is due to axonal injury; interpret it in conjunction with the rest of the NCS and EMG findings.

Severe axonal loss is defined as CMAP or SNAP amplitude below 25% of normal. Axonal injury can result in a corresponding reduction in conduction velocity down to 70-75% of normal, but not more than this. This is because even the slowest remaining axons with intact myelin sheaths will conduct at least 70-75% of normal conduction velocity. However, if the conduction velocity is less than 70% of normal, this suggests demyelination.

This concept is illustrated through the practical example in the table below. In both case 1 and 2 the conduction velocity is borderline reduced to 70% of normal. In case one, the amplitude is normal, thus the decreased conduction velocity likely represents demyelination. However, in case 2 the amplitude is significantly reduced and the conduction velocity is reduced, which indicates that there has been severe axonal loss, and that the surviving fibers are the slower conducting fibers.

Demyelinating pathology

Demyelination generally results in slowed conduction. The conduction velocity is decreased (nerves conduct more slowly), and distal latency is prolonged (the time taken to traverse a certain distance increases). Amplitude is relatively preserved unless there is conduction block, temporal dispersion, or secondary axon loss. Demyelination can be focal or homogenous, each of which show up differently on NCS and have separate differential diagnoses. Distal latency can be prolonged in demyelinating disorders even if the conduction velocity is normal, such as in early stages or mild cases of carpal tunnel syndrome.

Focal demyelination is usually seen in disorders such as compressive neuropathy, acquired demyelinating neuropathies like AIDP and CIDP, or a rare disorder known as multifocal motor neuropathy (MMN).

Homogeneous demyelination is seen in inherited demyelinating disorders such as Charcot-Marie-Tooth (CMT).

Focal demyelination I: Conduction Block

Conduction block is caused by segmental (patchy) demyelination or dysfunction of nodes of Ranvier, leading to reduction of saltatory conduction across subsequent nodes of Ranvier along the axon.  Notably, the actual myelin sheath and Schwann cells are not structurally disrupted; rather, they are functionally disrupted. Because a significant number of nerve action potentials just aren't conducted distal to the lesion, NCS has the appearance of axonal damage even though there is none. 

By definition, conduction block is a greater than >25-50% reduction in CMAP or SNAP amplitude or area with proximal stimulation. Conduction velocity is usually only mildly reduced.

For example: in the case of an ulnar neuropathy due to compression at the elbow joint, if there is conduction block you would see a normal CMAP when the nerve is stimulated at the wrist but decreased CMAP amplitude when the nerve is stimulated above the elbow. This is because nerve conduction from wrist onwards is normal, but nerve conduction across the elbow is not.

Figure 3.1: Examples of conduction block with normal CMAP on distal stimulation (e.g. wrist for ulnar nerve study) and significantly reduced CMAP amplitude on proximal stimulation (e.g. elbow for ulnar study).

Caveats to think through before diagnosing conduction block

• Is there correlating weakness or sensation loss on exam? If not, consider a technical problem with the study or anomalous anatomy.

• Is there temporal dispersion (see section below)? If yes, then we cannot prove conduction block since amplitude may be reduced due to temporal dispersion instead of conduction block. 

• Is the distal stimulation CMAP/SNAP very small? If yes, then it is difficult to reliably detect significant amplitude reduction and thus difficult to definitively diagnose conduction block.

• There are anatomical variants that can potentially lead to NCS misinterpretation. For example, in patients with Martin Gruber anastomoses that occur in the middle forearm, there may appear to be conduction block at either the median or ulnar nerve, when in reality there atypical anatomy is causing unexpected variations in nerve conduction.

Focal demyelination II: Temporal Dispersion

In patchy demyelination, different axons can be affected to different degrees. Thus, there will be variability in the conduction velocity amongst axons of a nerve, and thus stimulation of one nerve may result in different action potentials reaching the recording electrode at different times. In technical terms, there is loss of synchrony of nerve fiber action potentials. Therefore, when they are summed together, instead of one smooth SNAP, you see a string of small peaks (Figure 3.2). In technical terms, the interference pattern with proximal stimulation (summation of action potentials) has an abnormally prolonged duration, more peaks each with smaller amplitude, but the area under the waveform will be normal. Temporal dispersion is more often seen in sensory NCS, since motor nerves normally have 1) less variability in conduction velocities and 2) comparatively longer duration.

By definition, temporal dispersion is an increase in SNAP duration of ≥60% with proximal stimulation.

Figure 3.2: Examples of temporal dispersion block with normal CMAP on distal stimulation (e.g. wrist for ulnar nerve study) and CMAP on proximal stimulation (e.g. elbow for ulnar nerve) with significantly increased duration, increased number of peaks, and decreased amplitude.

Indeterminate results

• If there is both reduction in amplitude and prolonged duration with proximal stimulation, it can be hard to distinguish between conduction block and temporal dispersion. There are clinical and research guidelines for this scenario that are beyond the scope of this website.

• When a CMAP is small due to temporal dispersion or conduction block, EMG can assess for possible contribution of an axonal neuropathy.

Homogeneous demyelination

As the name suggests, in this scenario there is similar severity of demyelination of different axons both within and between nerves. There is no one segment of a nerve that is more affected than others. As a result, the conduction velocity is overall slow but there is no conduction block or temporal dispersion, since action potentials travel slowly but synchronously. 

Conduction velocity <50% of normal without evidence of focal demyelination is characteristic of inherited demyelinating disorders, primarily Charcot-Marie-Tooth (CMT). 

Caveats:

• Conduction slowing alone does not cause weakness - so why do patients with these disorders often present with weakness on exam? This is because there is usually secondary axon loss over time, leading to disability.

• So far the known exception to this rule is CMT-X, which can often have conduction block and/or temporal dispersion on NCS. Thus, patients presumed to have an inflammatory demyelinating polyneuropathy but remain refractory to treatment should be worked up for this.

Technical factors

There are technical factors that can affect the accuracy of NCS results. Some are modifiable (e.g. body temperature and skin contamination) and should be minimized. Others are non-modifiable (e.g. age and height), and NCS results should be interpreted accordingly.

1. Cold temperature (upper extremities should be >32° C, and lower extremities >30° C): 

   1. • Slowed conduction velocity

      • Prolonged distal latency

      • Increased amplitude and duration of SNAP and CMAP

2. Age > 60 years:

   1. • Slowed conduction velocity 

      • Prolonged late response (F wave and H reflex) latencies

      • Decreased amplitude of SNAP

3. Height (tall individuals with longer nerves and more tapering of nerves distally):

   1. • Longer late response (F wave and H reflex) latencies

      • Mildly decreased SNAP amplitudes

      • Mild slowing of conduction velocities

4. Skin contamination: 

   1. • Moisturizer, sweat, other substances can interfere with the test and cause stimulation artifact (when there is a large amplitude signal on nerve stimulation that obscures the actual SNAP/CMAP and therefore interferes with interpretation

Artifact

Electrical artifact from a variety of sources can lead to inaccurate or difficult to interpret waveforms. For example: 

• Nearby electronic devices like computers, phones, and monitors can cause artifact and should be switched off or put away if  possible.

• You may see "stimulus artifact" during motor NCS. Stimulus artifact looks like a high-amplitude, short-duration electrical spike that immediately follows electrical stimulation and obscures the early part of the  CMAP. This happens when the recording electrode detects the stimulus current directly rather than the muscle potential. You can minimize this artifact with good skin prep, increasing the distance between recording and stimulating electrodes, and placing the ground electrode between the recording and stimulating electrodes.

• Overstimulating a nerve can lead to co-stimulation of adjacent nerves and confound interpretation.

• Pacemakers, defibrillators, and deep brain stimulation devices.

NCS pathology: Self-test