Neuromuscular function can be disturbed at various levels, including: • Motoneuron or sensory neuron cell body
• Peripheral nerve axon • Peripheral nerve myelin • Neuromuscular junction • Muscle
The physiologic effect of each of these is summarized below and should be considered when individual disorders are discussed.
Neuron cell body dysfunction
Nerve cell body dysfunction is often due to neuronal degeneration, and the most
important disorders are ALS and SMA. We constantly lose neurons throughout our lives, but in these and other neuronal disorders, cellular death is accelerated. The neuronal
membranes become leaky so that there is influx of ions which depolarize the neurons. This depolarization may occasionally reach threshold, producing spontaneous action potentials in the neurons. In ALS, this is manifest as fasciculations.
The depolarization of the neuronal cell body results in activation of the voltage- dependent sodium channels, but these channels are also time-dependent – they become inactive after a short open time. The channels cannot open again until the membrane potential is re-established, so if this does not happen, they cannot be activated again. Therefore, the motoneurons become electrically inactive, contributing to the weakness. The influx of ions, especially calcium, into the neurons results in activation or enzymes including proteases and phospholipases which essentially digest the neurons from within. This causes neuronal death, so the denervated muscle fibers try to find innervation from surrounding surviving motor axons. Therefore, there are many more muscle fibers innervated by a single motor axon, which is manifest on EMG as giant potentials. The new nerve connections are not as fast or as consistent as the ones which developed in early life, so there is a variety of times from motor axon activation to muscle fiber activation which is manifest on EMG as polyphasic potentials.
Denervated muscle fibers develop their own fluctuations in membrane potential which can occasionally reach threshold. The single muscle fiber action potentials are the basis for fibrillation potentials and positive sharp waves. The difference between these two patterns is in geometry of action potential generation and recording, so there is not a pathological difference between these patterns.
NCS with motoneuron degenerations show reduced amplitude of the CMAP with little change in NCV, since the conduction of the fastest fibers is little affected. Sensory NCS is normal.
Peripheral nerve axon dysfunction
Axonal degeneration is the most common type of peripheral neuropathy, and there are a multitude of causes. The common feature is degeneration of the distal portion of the axon with denervation of the innervated muscle. This produces EMG changes which are similar to those described for neuronal degeneration, including polyphasic potentials, fibrillations, and positive sharp waves. While fasciculations can occur with axonal degenerations, this is not as common as with neuronal degenerations.
NCS with axonal denervation is characterized by reduced amplitude of the CMAP and SNAP, although the normal ranges of amplitude are so wide that amplitude, alone, may not be sufficient to detect an abnormality unless there is prominent axonal drop-out. NCVs are often normal but may be slightly slowed due to secondary demyelination. Axonal damage results in partial unraveling of the myelin sheath. If an axon is still functioning yet sick, the sheath may be dysfunctional enough to slow conductions. Peripheral nerve myelin dysfunction
Demyelination of peripheral nerves has a narrower differential diagnosis than axonal degenerations. The most important demyelinating conditions are autoimmune, including AIDP (GBS) and CIDP.
Damage to the myelin sheath of peripheral nerve produces prominent slowing of the propagation of action potentials. Normal axonal conduction is fast because the myelin sheath increases the impedance of the axonal membrane. Depolarization of the axon results in electrotonic conduction of the depolarization to the next node, or gap in the myelin sheath. The axon membrane at the node is capable of generating an action potential, but the membrane between the nodes, underneath the myelin sheath, is not. Electrotonic conduction is virtually instantaneous, compared with action potential
propagation, so with myelinated axons, the action potential essentially skips from node to node. This conduction is much faster than action propagation down an axon. The myelin sheath greatly reduces the decay in electrotonic conduction [diagram] which would normally occur, facilitating the fast conduction.
Demyelinating conductions destroy the increased transmembrane impedance which helps electrotonic conduction, so failure of conduction is common. This is seen on NCS as conduction block. The deterioration of the electrotonic conduction also causes marked slowing of conduction velocity. This slowing also results in an alteration in appearance of the compound action potential (CMAP and SNAP) termed dispersion.
EMG is often normal in patients with demyelinating neuropathy, especially early. However, with persistent demyelination there is secondary axonal damage, resulting in all of the features of denervation, discussed above. The findings are less prominent, and formation of long-duration polyphasics and giant potentials is not expected.
Neuromuscular junction dysfunction
Neuromuscular transmission is very secure in the absence of pathology; there is one muscle fiber action potential for every axon action potential. However, with
neuromuscular junction abnormalities, this synaptic security is compromised. The exact manifestation depends on the pathology. Reduced release of transmitter, as with botulism and Lambert-Eaton (myasthenic) syndrome results in failure of activation of the muscle fiber. This is manifest on NCS as reduced CMAP with normal NCV. Repetitive
stimulation at a fast rate can produce facilitation of transmitter release, thereby increasing the response, an incremental response. Myasthenia gravis is due to reduced numbers of available acetylcholine receptors, so there is also failure of muscle fiber activation. Repetitive stimulation does not help conduction, since some of the available receptors may be unable to bind to let another volley of acetylcholine. Therefore, repetitive stimulation results in successive less response. This is a decremental response. Muscle dysfunction
The most important myopathies are muscular dystrophies and inflammatory myopathies (polymyositis and dermatomyositis) Myopathies produce damage to the muscle fiber membrane. Changes in conductance to ions results in influx of sodium which can occasionally reach threshold. This produces fibrillation potentials and positive sharp waves which are indistinguishable from those of neuronal degenerations. However, the motor unit potentials differ. There is not reinnervation so there are no long-duration polyphasic potentials or giant potentials. Rather, each motor unit has fewer function muscle fiber potentials giving small motor unit action potentials. The conduction in the muscle fibers is dispersed, so that the muscle fiber potentials is somewhat separated. This gives rise to polyphasic potentials, but the duration is short since the change in
conduction is less than with axonal damage. Therefore, myopathic motor unit potentials are small-amplitude and short duration. This is called brief small-amplitude polyphasic potentials (BSAPPs).
Equipment
Equipment used in electrophysiological assessment of nerve and muscle is similar in overall design and function. Most equipment is essentially a computer with interface card for signal acquisition and controlling a stimulator. The stimulator is a waveform
generator controlled by a controller module in the computer. The acquisition equipment consists of amplifiers, wide-band filters, and is external to the computer, itself. The output from the acquisition equipment is then fed to an analog-to-digital conversion module of the computer.