AXON REFLEXES:

A reflex is an involuntary, immediate, automatic and

stereotyped response to a specific sensory stimulation. Sir Thomas Lewiss explanation of the flare component of the triple response. This response, consisting sequentially of the red line, flare, and wheal, can readily be produced by scratching the skin with a blunted point.

 According to Lewis, the flare was due to dilatation of

neighboring arterioles, this in turn having been triggered by a local nervous system.

Reflex arc
There is a sensory receptor at the starting point of reflex

arc, an effector at the final point and an integration center between them. An afferent pathway connects the sensory receptor to the integration center. An efferent pathway connects the integration center to the effector. There is one or more synapses in a reflex arc. Sensory receptors and neurons: Sensory neurons which transmit impulses toward the central nervous system from sensory receptors. Central process is known as central branch, axonal branch, central axon and axon.

 Peripheral process is also known as peripheral branch,

dendritic branch, peripheral axon, and dendrit. When a sensory receptor is stimulated it initiates a signal that is carried to the central nervous system by processes of sensory neurons. Physiopathology: It is included in physiopathological processes from regulation of skin blood flow and sweating to inflammation and pain, from itch to asthma bronchiale and allergic rhinitis. It is proposed that axon reflexes are responsible from some effects of acupuncture which is a complementary technique for analgesia.

 The effect of axon reflex to skin blood vessels is

monitored measuring the skin blood flow by laser doppler. Axon reflex test are useful for monitoring the effects of axon reflexes on sweat glands. Measurements of effects of axon reflexes are important for neuropathies like as pre-diabetic and diabetic neuropathy.

Clinical importance:
Axon reflex mechanism therapy is effective for itch and

pain. Axon reflex mechanism is important for physiopathology of allergic rhinitis and sinusitis & inflammation.
In bronchial asthma release of sensory neuropeptides

such as substance P, neurokinin A, and calcitonin generelated peptide are potent inducers of airway smooth muscle contraction, bronchial oedema, extravasation of plasma, mucus hypersecretion, and possibly inflammatory cell infiltration and secretion by axon reflex mechaism.

REPETITIVE NERVE STIMULATION

INTRODUCTION:
Nerve stimulation techniques as tests for neuromuscular

transmission. It began with Jolly (1895) who applied faradic current repeatedly at short intervals by using a kymographic recording and visual inspection of skin displacement. He found that the size of the muscle response deteriorated rapidly in patients with myasthenia gravis during the faradization. His equipment consisted of a double-coil stimulator capable of eliciting only submaximal responses and a mechanical, rather than electrical, recorder.

Myasthenia gravis: It causes muscle paralysis because of inability of the neuromuscular junctions to transmit enough signals from the nerve fibers to the muscle fibers.
Myasthenia gravis is an autoimmune disease in which the

patients have developed immunity against their own acetylcholine-activated ion channels.

 Regardless of the cause, the end plate potentials that

occur in the muscle fibers are mostly too weak to stimulate the muscle fibers in myasthenia gravis. Faradic current failed to elicit a response in the volitionally fatigued muscle prior to testing. Conversely, after faradization, muscle responded poorly to subsequent volitional contraction. Based on these findings, he concluded that the myasthenics had motor failure of the peripheral, rather than central, nervous system.

 The use of supermaximal stimulation and the recording of

the muscle action potential have increased the reliability and sensitivity of nerve stimulation techniques considerably.
Later studies have established optimal frequency of

stimulation, proper control of temperature, appropriate selection of muscles, and various activation procedures to enhance an neuromuscular block.

 Microelectrode studies provide direct recording of end-

plate potentials from Muscle

Other electrophysiologic methods assess the

neuromuscular junction only indirectly.

such an approach allows quantitation of the motor

response to paired stimuli, tetanic contraction, or repetitive stimulation at fast and slow rates

Use:
Transmission defects affect a variety of disease states,

such as myasthenia gravis, myasthenic syndromes, botulism, amyotrophic lateral sclerosis, poliomyelitis, and multiple sclerosis.

METHODS AND TECHNICAL FACTORS

Belly-Tendon Recording Belly-tendon recording consists of stimulating the nerve with supramaximal intensity and recording the muscle action potential with the active electrode (G1) placed over the motor point and the reference electrode (G2) on the tendon.

 The initially negative potential thus recorded represents

the summated electrical activity from the entire muscle fiber population, discharging relatively synchronously. The area under the negative phase changes primarily with the number of muscle fibers activated. The magnitude of the unit discharge from individual muscle fibers also alters the size of the compound muscle potential, especially in myogenic disorders.

Movement-Induced Artifacts
Movement-related artifacts abound during repetitive

stimulation of the nerve. The recording electrode may continuously slide away from the muscle belly, or the stimulating electrodes may gradually slip from the nerve, causing subthreshold activation.

 Changes in limb position and the spatial relationship of

muscle and recording electrodes, does alteration in amplitude of the recorded response
Firm immobilization of the limb together with visual

inspection of the contracting muscle under study minimizes the movement induced variability.

Alteration in thumb position from abd to add. after each shock gave rise to a smooth reduction in amplitude with concomitant increase in duration of successive potentials. The area under the waveform showed relatively little change from the 1st to the 5th response.

 Artifacts cause abrupt, irregular changes in the amplitude

or shape of the evoked response. Some movement artifacts, however, induce a smooth, progressive alteration of amplitude that closely mimics the myasthenic response.
Nevertheless, close scrutiny often discloses

accompanying changes in duration or other aspects of Waveform.

Temperature and Other Factors

Exposure to warm sunlight may precipitate ptosis and

diplopia in myasthenic patients. Similarly, electrophysiologic abnormalities of weak muscles may appear only after local warming.
Physiologic mechanisms that account for the improved

neuromuscular transmission with cooling include-

1. Facilitated transmitter replacement in the presynaptic terminal

2. reduced amount of transmitter release at the neuromuscular junction by the first of a train of impulses, leaving more quanta available for subsequent stimuli 3. decreased hydrolysis of acetylcholine (ACh) by acetyl cholinesterase, allowing sustained action of the transmitter already released from the axon terminal 4.increased postsynaptic receptor sensitivity to Ach 5.reduced rate of removal of calcium ions (Ca2+) from the nerve terminal after stimulation.

 Elevated body temperature up to 42 C causes no

abnormality in healthy subjects, but enhances the decrement on repetitive nerve stimulation in patients with myasthenia gravis.
From 35 to 28 C increases the amplitude of the

compound muscle action potential and enhances the force of the isometric twitch and tetanic contraction. Patients with the myasthenic syndrome also experience distinct improvement after cooling

 Cooling reduces the decrement to repetitive nerve

stimulation but causes increase in amplitude.

 The effect of cholinesterase inhibitors also influences the

results of repetitive stimulation.

Administration of anticholinesterase drugs within a few

hours before the test reduces the probability of obtaining a decremental response.
With an overdose of anticholinesterase drugs, a single

nerve impulse may cause a repetitive muscle response, and repetitive stimuli at a high rate give rise to a decremental response.

COMMONLY USED NERVES AND MUSCLES

Distal Versus Proximal Muscle
Patients with myasthenia gravis rarely have a decremental response in clinically unaffected muscle. Weak proximal or facial muscles show a higher incidence of electrical abnormality than stronger distal muscles. Studies of the distal musculature provide technically more reliable results than those of more proximal muscles in the limb or facial muscles.

RECOVERY CURVES BY PAIRED STIMULATION

Short Interstimulus Intervals A second stimulus delivered within a few milliseconds evokes a smaller response, indicating refractoriness of the nerve and muscle (see Fig.) The second potential then progressively recovers, with some overlap of the two responses at intervals of less than 15 ms. In typical cases of myasthenia gravis, the first stimulus elicits a maximal or near-maximal muscle response. The recovery curve also follows a normal pattern for short interstimulus intervals up to 15 ms.

Fig: Compound action potentials from the thenar muscles elicited by paired shocks delivered to the median nerve at the wrist. Time intervals ranged from 2 to 30 ms between conditioning and test stimuli.

Long Interstimulus Intervals Despite the release of a greater amount of acetylcholine (ACh), the second muscle potential normally shows no increment from the already maximal first response.
Most patients with myasthenia gravis or botulism also

have minimal change at this interstimulus range. In contrast, patients with myasthenic syndrome show an increment at interstimulus intervals ranging from 15 to 100 ms as one of the most characteristic electrophysiologic features.
The decremental response in myasthenia gravis begins at

intervals of about 20 ms but becomes more definite at intervals between 100 and 700 ms. The response reaches the trough at an interstimulus interval of about 300-500 ms

DECREMENTAL RESPONSE AT SLOW RATES OF STIMULATION

Normal Muscles Repetitive stimulation at a rate of 1-5 Hz depletes the immediately available acetylcholine (ACh) store, without superimposed facilitation from neurosecretory mechanisms. In normal muscles, decrement at stimulation of 2-3 Hz, if present, does not exceed 5-8 percent.

 In myasthenia gravis, the amplitude drops maximally

between the first and second responses of a train, followed by a further but lesser decline up to the fourth or fifth potential. Occasionally, the recovery may even exceed the original value by 10-20 percent, especially after several seconds of repetitive stimulation. More characteristically, continued stimulation induces a long, slow decline after a transient increment.

Fig: slight decrement at slow rates of stimulation up to five per second, and progressively more prominent increment at faster rates of 10-30 per second.

INCREMENTAL RESPONSE AT FAST RATES OF STIMULATION

Normal Muscles Supramaximal stimulation normally activates all muscle fibers innervated by the nerve. This precludes any increment in response to greater amounts of acetylcholine (ACh) released by subsequent stimuli. In normal adults, muscle action potentials remain stable during repetitive stimulation at a rate of up to 20-30 Hz. Some healthy infants, however, may show a progressive decline in amplitude at this rate.

 In the myasthenic syndrome single stimuli typically elicit a

strikingly small compound muscle action potential (See Fig.)The amplitude varies over a wide range among different subjects. Repetitive stimulation given at 20-50 Hz induces a remarkable increment of successive muscle action potentials to a normal or near normal Level An incremental response, though characteristic of the myasthenic syndrome and Botulism.

The histogram plots the amplitude of the hypothenar muscle potential elicited by single maximal stimuli to the ulnar nerve. The scale on the abscissa denotes normal strength (0), 75 percent (1), 50 percent (2), 25 percent (3), and complete paralysis (4) in MG patient.

EFFECT OF TETANIC CONTRACTION

Use of Prolonged Stimulation A short train of several shocks at a slow rate suffices for routine evaluation of neuromuscular transmission. Prolonged stimulation at a rapid rate adds diagnostic information in the evaluation of infantile Botulism Tetany develops after electrical stimulation of a 20-30 s train at 50 Hz or a continuous run for a few minutes at 3 Hz.

CHANGES IN MYOGENIC DISORDERS

A train of stimuli causes an apparent decrement of the

compound muscle action potentials in a number of myogenic disorders, such as McArdle's disease, myotonia, pararnyotonia congenita, and periodic paralysis.