Electrophysiologic study of the peripheral nervous system typically involves nerve conduction studies (NCS) and needle examination of the muscle (electromyography; EMG). NCS/EMG is useful to localize a lesion (root/plexus/nerve/neuromuscular junction/muscle) and may also characterize the specific pathology (e.g., demyelinating vs. axonal pathology). Note that the presence of multiple coexisting pathologies—for example, a myopathy in conjunction with diabetic neuropathy—will limit the applicability of this algorithm.
When reviewing NCS, sensory responses are examined first. In the setting of sensory symptoms or findings of sensory loss on examination, normal sensory responses localize the lesion proximal to the dorsal root ganglion (DRG) of the sensory neuron. Lesions distal to the DRG cause disconnection between the distal sensory axon and the cell body, resulting in Wallerian degeneration. This results in low amplitude or absent sensory responses. In radiculopathy or central nervous system lesions, the DRG and the distal axon are preserved, resulting in normal sensory responses.
In patients with weakness but no sensory symptoms and normal sensory responses, localization can be narrowed to the lower motor neuron cell bodies, motor nerves, neuromuscular junction (NMJ), or muscle.
While rare, isolated demyelination of the motor neurons (multifocal motor neuropathy; MMN) may clinically mimic anterior horn cell disease. MMN causes slowly progressive asymmetric weakness, typically beginning in the upper extremities. Anti-GM1 bodies are seen in some but not all patients. Conduction block is the demyelinating feature most frequently described.
The prototypical postsynaptic NMJ disorder is myasthenia gravis, which typically presents with fluctuating weakness and bulbar or ocular symptoms (e.g., double vision). In generalized myasthenia gravis, 2-Hz repetitive stimulation demonstrates decremental motor response amplitudes in ~ 80% of patients. With each successive stimulation in the first second, less acetylcholine is released, resulting in the reduced motor amplitudes.
Diffuse reduction of motor response amplitudes with spared sensory responses suggests either diffuse motor neuron dysfunction without sufficient collateral sprouting, as can be seen in advanced amyotrophic lateral sclerosis, or a presynaptic disorder of the NMJ such as Lambert-Eaton myasthenic syndrome (LEMS). LEMS is an autoimmune disease often associated with small cell lung cancer. LEMS presents with leg greater than arm weakness without significant muscle atrophy along with autonomic dysfunction, such as dry mouth. Testing for presynaptic disorders should be performed in all patients with diffusely reduced motor amplitudes. Similar to postsynaptic NMJ disorders, slow (2 Hz) repetitive stimulation produces a decrement in motor response amplitudes; however, LEMS can be distinguished by a > 100% increase in the amplitude of the motor response following a brief period of exercise (10 seconds) of the affected muscle.
In patients with normal NCS and needle EMG, most peripheral nervous system issues can be excluded. One exception is myasthenia gravis with limited generalized symptoms (e.g., ocular myasthenia).
Myopathic features include small amplitude motor units with early recruitment. On a physiologic basis these small units are explained by the loss of myocytes that contribute to the electrical potential of a motor unit. Loss of myocytes results in ineffective force generation by individual motor units, resulting in early recruitment of several units to generate the required force.
Denervation on needle EMG manifests as reduced motor unit recruitment and abnormal spontaneous muscle activity in the form of fibrillation potentials and positive sharp waves. Reduced motor unit recruitment results from the loss of motor neurons and manifests as an increase in the firing frequency of the remaining motor neurons; this finding is present immediately. Fibrillation potentials and positive sharp waves start several weeks after denervation. While often associated with neurogenic disease, fibrillation potentials and positive sharp waves can also be seen in myopathic processes with fiber splitting, resulting in partial denervation of the affected myocytes (e.g., inflammatory myopathies). Chronic reinnervation results in large amplitude motor units, as remaining motor neurons will collaterally sprout to denervated myocytes. These findings appear several months after a denervating injury.
On motor NCS, there are two measures of conduction speed: (1) the speed of conduction between the distal stimulation site and the muscle, assessed by distal motor latency; and (2) the speed of conduction between stimulation sites, assessed by conduction velocity. In focal nerve compression, only one of these two parameters will be abnormal, localizing the site of compression. For example, the median distal motor latency would be prolonged in moderate carpal tunnel syndrome, but the median nerve conduction velocity would be normal.
Conduction speed is determined by the presence of myelin and large diameter axons. The electrophysiologic criteria for demyelination is shown in the flowchart. Conduction block is defined as ≥ 50% reduction of the proximal amplitude compared to the distal amplitude. Loss of large-diameter axons will result in mildly slowed conduction but will not meet criteria for demyelination.
When multiple compressive neuropathies are seen, consider diabetic polyneuropathy, amyloidosis, and, if a family history is present, hereditary neuropathy with liability to pressure palsies (HNPP).
The involvement of multiple nerves in an asymmetric, non–length-dependent pattern is referred to as mononeuropathy multiplex and requires assessment for autoimmune and inflammatory conditions. A mononeuropathy outside of typical compression site or multiple mononeuropathies in one limb should prompt consideration of a mass lesion or brachial neuritis.