Adverse effects
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Repetitive nerve stimulation is a variant of the nerve conduction study where electrical stimulation is delivered to a motor nerve repeatedly several times per second. By observing the change in the muscle electrical response (CMAP) after several stimulations, a physician can assess for the presence of a neuromuscular junction disease, and differentiate between presynaptic and postsynaptic conditions. The test was first described by German neurologist Friedrich Jolly in 1895, [1] and is also known as Jolly's test. [2]
Repetitive nerve stimulation is used to diagnose neuromuscular junction (NMJ) disorders, the most common of which is myasthenia gravis. A decremental response (a smaller and smaller muscle response with each repetitive stimulus) is abnormal and indicates NMJ dysfunction. This can be further confirmed if the response normalizes after administration of edrophonium or neostigmine. [1]
Stimulation of a motor neuron causes it to release acetylcholine, which is stored up in vesicles at the axon terminal. The acetylcholine binds to nicotinic receptors on the muscle fiber, which open sodium channels and depolarizes the muscle cell.
As nerve stimulation is rapidly repeated, the acetylcholine stored in the nerve terminal is gradually depleted, and there is a slight weakening of the acetylcholine signal sent to the muscle fiber, resulting in smaller endplate potentials (EPPs). In normal muscle, although the EPPs become smaller with repetitive stimulation, they remain above the threshold needed to trigger muscle contraction. In myasthenia gravis, where many of the acetylcholine receptors are blocked, the EPP may exceed the threshold initially, but quickly falls below threshold with repetitive stimulation, resulting in the muscle fiber failing to contract. As one by one the muscle fibers fail to contract, the overall CMAP measured grows smaller and smaller, leading to the pathologic decremental response.
As with all nerve conduction studies, the body part tested should be clean, free of lotions and conductive substances, with jewelry removed. It is best to advise patients to refrain from taking acetylcholinesterase inhibitors (e.g., Pyridostigmine Mestinon) for 6–8 hours before the study, unless medically contraindicated. These agents make more ACH available to bind at the ACHRs and may potentially diminished CMAP decrement, resulting in a normal study (false negative).
If the electrode is not properly immobilized, the result is a change in the CMAP amplitude which may lead to misinterpretation. So the recording electrodes should be secured well with tape, the stimulator secured with a Velcro strap and the entire hand with pad or board. The goal is to minimize the movement of the limb. Impulse transmission: Submaximal stimulation can give artifactual decrement or increment in the CMAP amplitude. So always check to ensure that the stimulus is supramaximal before beginning of RNS.
A peripheral nerve is electrically stimulated, and the amplitude of the CMAP is recorded at rest and after a short voluntary activation. The stimulation frequency is 3 Hz, the number of stimuli 10. The result is reported as the difference in amplitude of the CMAP between stimulation one and four (in %). The area value changes typically in parallel, but is not reported. If there is a major difference between amplitude and area decrement, technical factors should be considered.
Recording protocol:
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In neuroscience, an F wave is one of several motor responses which may follow the direct motor response (M) evoked by electrical stimulation of peripheral motor or mixed nerves. F-waves are the second of two late voltage changes observed after stimulation is applied to the skin surface above the distal region of a nerve, in addition to the H-reflex which is a muscle reaction in response to electrical stimulation of innervating sensory fibers. Traversal of F-waves along the entire length of peripheral nerves between the spinal cord and muscle, allows for assessment of motor nerve conduction between distal stimulation sites in the arm and leg, and related motoneurons (MN's) in the cervical and lumbosacral cord. F-waves are able to assess both afferent and efferent loops of the alpha motor neuron in its entirety. As such, various properties of F-wave motor nerve conduction are analyzed in nerve conduction studies (NCS), and often used to assess polyneuropathies, resulting from states of neuronal demyelination and loss of peripheral axonal integrity.
Lambert–Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder characterized by muscle weakness of the limbs.
Myasthenia gravis (MG) is a long-term neuromuscular junction disease that leads to varying degrees of skeletal muscle weakness. The most commonly affected muscles are those of the eyes, face, and swallowing. It can result in double vision, drooping eyelids, trouble talking, and trouble walking. Onset can be sudden. Those affected often have a large thymus or develop a thymoma.
In neuroscience, an excitatory postsynaptic potential (EPSP) is a postsynaptic potential that makes the postsynaptic neuron more likely to fire an action potential. This temporary depolarization of postsynaptic membrane potential, caused by the flow of positively charged ions into the postsynaptic cell, is a result of opening ligand-gated ion channels. These are the opposite of inhibitory postsynaptic potentials (IPSPs), which usually result from the flow of negative ions into the cell or positive ions out of the cell. EPSPs can also result from a decrease in outgoing positive charges, while IPSPs are sometimes caused by an increase in positive charge outflow. The flow of ions that causes an EPSP is an excitatory postsynaptic current (EPSC).
A neuromuscular junction is a chemical synapse between a motor neuron and a muscle fiber.
Electromyography (EMG) is a technique for evaluating and recording the electrical activity produced by skeletal muscles. EMG is performed using an instrument called an electromyograph to produce a record called an electromyogram. An electromyograph detects the electric potential generated by muscle cells when these cells are electrically or neurologically activated. The signals can be analyzed to detect abnormalities, activation level, or recruitment order, or to analyze the biomechanics of human or animal movement. Needle EMG is an electrodiagnostic medicine technique commonly used by neurologists. Surface EMG is a non-medical procedure used to assess muscle activation by several professionals, including physiotherapists, kinesiologists and biomedical engineers. In Computer Science, EMG is also used as middleware in gesture recognition towards allowing the input of physical action to a computer as a form of human-computer interaction.
End plate potentials (EPPs) are the voltages which cause depolarization of skeletal muscle fibers caused by neurotransmitters binding to the postsynaptic membrane in the neuromuscular junction. They are called "end plates" because the postsynaptic terminals of muscle fibers have a large, saucer-like appearance. When an action potential reaches the axon terminal of a motor neuron, vesicles carrying neurotransmitters are exocytosed and the contents are released into the neuromuscular junction. These neurotransmitters bind to receptors on the postsynaptic membrane and lead to its depolarization. In the absence of an action potential, acetylcholine vesicles spontaneously leak into the neuromuscular junction and cause very small depolarizations in the postsynaptic membrane. This small response (~0.4mV) is called a miniature end plate potential (MEPP) and is generated by one acetylcholine-containing vesicle. It represents the smallest possible depolarization which can be induced in a muscle.
Electroneuronography or electroneurography (ENoG) is a neurological non-invasive test used to study the facial nerve in cases of muscle weakness in one side of the face. The technique of electroneuronography was first used by Esslen and Fisch in 1979 to describe a technique that examines the integrity and conductivity of peripheral nerves. In modern use, ENoG is used to describe study of the facial nerve, while the term nerve conduction study is employed for other nerves.
A nerve conduction study (NCS) is a medical diagnostic test commonly used to evaluate the function, especially the ability of electrical conduction, of the motor and sensory nerves of the human body. These tests may be performed by medical specialists such as clinical neurophysiologists, physical therapists, chiropractors, physiatrists, and neurologists who subspecialize in electrodiagnostic medicine. In the United States, neurologists and physiatrists receive training in electrodiagnostic medicine as part of residency training and in some cases acquire additional expertise during a fellowship in clinical neurophysiology, electrodiagnostic medicine, or neuromuscular medicine. Outside the US, clinical neurophysiologists learn needle EMG and NCS testing.
Ocular myasthenia gravis (MG) is a disease of the neuromuscular junction resulting in hallmark variability in muscle weakness and fatigability. MG is an autoimmune disease where anomalous antibodies are produced against the naturally occurring acetylcholine receptors in voluntary muscles. MG may be limited to the muscles of the eye, leading to abrupt onset of weakness/fatigability of the eyelids or eye movement. MG may also involve other muscle groups.
A cholinergic crisis is an over-stimulation at a neuromuscular junction due to an excess of acetylcholine (ACh), as a result of the inactivity of the AChE enzyme, which normally breaks down acetylcholine.
Rheobase is a measure of membrane potential excitability. In neuroscience, rheobase is the minimal current amplitude of infinite duration that results in the depolarization threshold of the cell membranes being reached, such as an action potential or the contraction of a muscle. In Greek, the root rhe translates to "current or flow", and basi means "bottom or foundation": thus the rheobase is the minimum current that will produce an action potential or muscle contraction.
Chronaxie is the minimum time required for an electric current double the strength of the rheobase to stimulate a muscle or a neuron. Rheobase is the lowest intensity with indefinite pulse duration which just stimulated muscles or nerves. Chronaxie is dependent on the density of voltage-gated sodium channels in the cell, which affect that cell’s excitability. Chronaxie varies across different types of tissue: fast-twitch muscles have a lower chronaxie, slow-twitch muscles have a higher one. Chronaxie is the tissue-excitability parameter that permits choice of the optimum stimulus pulse duration for stimulation of any excitable tissue. Chronaxie (c) is the Lapicque descriptor of the stimulus pulse duration for a current of twice rheobasic (b) strength, which is the threshold current for an infinitely long-duration stimulus pulse. Lapicque showed that these two quantities (c,b) define the strength-duration curve for current: I = b(1+c/d), where d is the pulse duration. However, there are two other electrical parameters used to describe a stimulus: energy and charge. The minimum energy occurs with a pulse duration equal to chronaxie. Minimum charge (bc) occurs with an infinitely short-duration pulse. Choice of a pulse duration equal to 10c requires a current of only 10% above rheobase (b). Choice of a pulse duration of 0.1c requires a charge of 10% above the minimum charge (bc).
Dok-7 is a non-catalytic cytoplasmic adaptor protein that is expressed specifically in muscle and is essential for the formation of neuromuscular synapses. Further, Dok-7 contains pleckstrin homology (PH) and phosphotyrosine-binding (PTB) domains that are critical for Dok-7 function. Finally, mutations in Dok-7 are commonly found in patients with limb-girdle congenital myasthenia.
Motor unit number estimation (MUNE) is a technique that uses electromyography to estimate the number of motor units in a muscle.
Neuromuscular junction disease is a medical condition where the normal conduction through the neuromuscular junction fails to function correctly.
Clinical electrophysiology is the application of electrophysiology principles to medicine. The two main branches of this discipline are electrotherapy and electrophysiologic testing Clinical electrophysiology can be utilized in the study and treatment of various physiological conditions, and most notably in clinical cardiac electrophysiology.
A depolarizing prepulse (DPP) is an electrical stimulus that causes the potential difference measured across a neuronal membrane to become more positive or less negative, and precedes another electrical stimulus. DPPs may be of either the voltage or current stimulus variety and have been used to inhibit neural activity, selectively excite neurons, and increase the pain threshold associated with electrocutaneous stimulation.
Somatosensory evoked potential is the electrical activity of the brain that results from the stimulation of touch. SEP tests measure that activity and are a useful, noninvasive means of assessing somatosensory system functioning. By combining SEP recordings at different levels of the somatosensory pathways, it is possible to assess the transmission of the afferent volley from the periphery up to the cortex. SEP components include a series of positive and negative deflections that can be elicited by virtually any sensory stimuli. For example, SEPs can be obtained in response to a brief mechanical impact on the fingertip or to air puffs. However, SEPs are most commonly elicited by bipolar transcutaneous electrical stimulation applied on the skin over the trajectory of peripheral nerves of the upper limb or lower limb, and then recorded from the scalp. In general, somatosensory stimuli evoke early cortical components, generated in the contralateral primary somatosensory cortex (S1), related to the processing of the physical stimulus attributes. About 100 ms after stimulus application, additional cortical regions are activated, such as the secondary somatosensory cortex (S2), and the posterior parietal and frontal cortices, marked by a parietal P100 and bilateral frontal N140. SEPs are routinely used in neurology today to confirm and localize sensory abnormalities, to identify silent lesions and to monitor changes during surgical procedures.
Electromyoneurography (EMNG) is the combined use of electromyography and electroneurography This technique allows for the measurement of a peripheral nerve's conduction velocity upon stimulation (electroneurography) alongside electrical recording of muscular activity (electromyography). Their combined use proves to be clinically relevant by allowing for both the source and location of a particular neuromuscular disease to be known, and for more accurate diagnoses.