A typical stimulating electrode is one with an anode and a cathode in the form of two blunt prongs which are applied to the skin surface overlying the nerve. In Figure 12.1 it has been placed over the median nerve at the wrist (just lateral to the cordlike palmaris longus tendon). The cathode is placed nearer to the recording site than the anode in order to prevent any conduction block by the anode. When sufficient current is passed from cathode to anode, transmembrane ionic movements initiate impulse propagation in both directions along the nerve. Large myelinated nerve fibers lying nearest the cathode are the first to become depolarized; these include the Aα diameter axons of anterior horn motor neurons. A pulse of 20–40 mA with a duration of 0.1 ms is usually sufficient to activate all motor units in abductor pollicis brevis.

Figure 12.1 Basic setup for recording compound motor action potentials (CMAPs). SA, stimulus artifact. The stimulating electrode (S) has been placed over the median nerve. The active electrode (Act) has been placed over the abductor pollicis brevis muscle and the reference (Ref) electrode has been placed distally.

Recording

An active surface recorder, in the form of a disk in this situation, is placed over the midregion of the muscle where the motor end plates are concentrated, i.e. the motor point. A second, reference electrode, is placed over a neutral site a short distance away. The amplifier used to magnify evoked motor responses is designed to record the potential differences between the two sites. The setup is arranged so that if the active electrode records a more negative response this will take the form of an upward deflection on the monitor.

At low level of stimulation, the only on-screen change in the tracing will be a small stimulus artifact on an otherwise flat tracing. As the current increases, small compound motor action potentials appear. These are produced by activation of large myelinated axons close to the stimulator; the depolarization wave traveling along each will in turn depolarize all of the muscle fibers in the territory of that axon. In the case of the intrinsic muscles of the hand, including abductor pollicis brevis, each motor unit has an innervation ratio of two or three hundred muscle fibers per motor neuron. In large muscles not specialized for fine movements (e.g., deltoid, gastrocnemius) the minimum deflection on the monitor will be several times larger, for two reasons: their motor innervation ratio is 1/1000 or more, and their larger muscle fibers generate action potentials of greater amplitude.)

It should be emphasized that the onscreen waveform is not produced by the contraction process itself, but by the extracellular potentials generated by depolarization of the muscle membranes and filtered through the tissues and skin. However, while this distinction needs to be remembered, most disorders of muscle will also affect the surface membrane depolarization and hence lead to abnormalities of the waveform morphology.

Increasing the applied voltage activates additional motor units until all are activated by each pulse. The required stimulus is called maximal. For good measure, the final stimulus is often supramaximal at 5–10% above maximal. The final waveform observed constitutes the compound motor action potential, or CMAP. It is produced by summation of the individual muscle fiber potentials (Figure 12.2).

Figure 12.2 Summation of CMAPs. Motor units are simply represented by interdigitating pairs of muscle fibers. Moderate (1), medium (2) and maximal (3) stimulation yield progressively larger waveforms on screen, despite being physiologically separate phenomena.

Routine measurements of the final CMAP are shown in Figure 12.3. They include the latency (time interval) between stimulus and depolarization onset, and the amplitude and duration of the negative phase of the waveform. (The final, positive phase is produced by inward ion movement during collective repolarization of the muscle fibers.)

Figure 12.3 Routine CMAP measurements.

Motor nerve conduction velocity (MNCV)

The setup required to determine motor nerve conduction velocity for the median nerve is straightforward, as shown in Figure 12.4. Here the nerve has first been activated at the wrist (S1) to generate and store a ‘wrist to muscle’ velocity record. The stimulator has then been placed over the median nerve at the elbow (S2) to provide an ‘elbow to muscle’ record. Speed being the product of distance over time, the elbow-to-wrist conduction velocity is given by subtracting one value from the other, as illustrated by the case example.

Figure 12.4 Calculation of motor nerve conduction velocity. The same stimulator is used twice: S1 means 1st stimulus and S2 is 2nd stimulus. The double arrows represent the two length measurements. The time baseline is not included. At bottom is an example yielding a normal conduction velocity.

Second choice

It may be considered wise to perform a confirmatory MNCV on another nerve. The ulnar is the standard second choice: S1 is performed over the nerve at the wrist just lateral to flexor carpi ulnaris, S2 where the nerve emerges from behind the medial epicondyle. The active recorder is applied over the hypothenar muscles at the medial margin of the palm.

Sensory nerve conduction

For studies of sensory nerve conduction velocity (SNCV), the median is again the nerve of choice (Figure 12.5). Again it is large myelinated nerve fibers that will be stimulated, and the site and manner of stimulation at elbow and wrist will be the same. On this occasion, however, we are selectively recording antidromic stimulation of cutaneous sensory fibers – specifically, of the digital branches of the median nerve to the skin of the index finger, which is wearing an active recorder in the form of a ring.

Figure 12.5 Calculation of sensory nerve conduction velocity (SNCV). Digital branches of the median nerve are represented. The basic principles for the calculation are the same as for MNCV studies. For the asterisks see main text.

The prime function of the myelinated nerve fibers to be sampled by the ring recorder are those supplying the highly sensitive and discriminatory skin of the finger pad, described in Chapter 11. The largest, serving Meisssner and Pacinian corpuscles and Merkel cell–neurite complexes, are known to normally conduct at a speed of 60–100 m/s and the finest, serving mechanical nociceptors, at 10–30 m/s. This tenfold variation is in marked contrast to that of the relatively uniform fiber size of the stem axons supplying the small motor units of the abductor muscle and conducting at 45–55 m/s. One consequence is that, when stimulating sensory nerves at increasing distances from the recording site, a change in the waveform shape is normally noted. In the figure, the asterisks are intended to highlight the difference in the shape of the waveforms of the two compound sensory nerve action potentials (CSNAPs). Two factors are involved:

1 Physiologic temporal dispersion. As runners in a race become progressively separated over distance, the fastest impulse conductors take the lead and the slowest trail behind, with consequent elongation of the CSNAP profile over the longer test distance, caused by this temporal dispersion (scattering over time).

2 Phase cancellation. The later waveform is also flatter. This is explained in part by the phenomenon whereby positive and negative phases of adjacent waveforms tend to cancel each other out. It should be emphasized that this phase cancellation is not a physiological event: the waves themselves are not affected by the ‘eavesdropper’ wrapped around the finger close to the finishing line. An additional factor is the diminishing amount of phase summation being recorded with increasing separation of action potentials.

Sensory nerve conduction velocity (SNCV)

The basic modes of operation and calculation are the same as shown for the MNCV study. A case example is included in Figure 12.5 which demonstrates phase cancellation from temporal dispersion.

Second choice

Again, the ulnar nerve is the standard second choice. Ulnar nerve stimulation is performed at wrist and elbow as before, with a ring recorder is slipped onto the little finger.

Nerve conduction in the lower limb

The lower limb muscle most frequently sampled for motor nerve conduction velocity is extensor digitorum brevis on the dorsum of the foot (Figure 12.6). The deep peroneal nerve is stimulated first in front of the ankle and then at the level of the neck of the fibula. At times, tibialis anterior is also sampled; in this case the nerve is stimulated first at the neck of the fibula and then at the lateral edge of the popliteal fossa next to the biceps femoris tendon.

Figure 12.6 Positions of recorder and stimulator for measurement of MNCV for the peroneal nerve.

A second choice for MNCV is the tibial nerve recording from adductor hallucis, located on the medial side of the foot (Figure 12.7A).

Figure 12.7 (A) Positions of recorder and stimulator for MNCV study of the tibial nerve. (B) Positions for antidromic recording of SNCV for the sural nerve.

For SNCV assessment, the sural is the nerve of choice. The sural arises from the tibial and receives a contribution from the peroneal; it supplies the skin along the lateral margin of the foot. The recorder is applied to the skin below the lateral malleolus, and the nerve is stimulated antidromically at the levels shown in Figure 12.7B.

Nerve root pathology

Nerve root pathology is known as radiculopathy (L. radix, ‘root’). Radiculopathies are encountered:

• in the neck, where roots of spinal nerves C6 and C7 are especially prone to being pinched by osteophytes generated by cervical spondylosis, as explained in Clinical Panel 12.1;

• in the lower back, where the nerve roots of S1 are especially prone to compression by a prolapsed L5/S1 intervertebral disk, also explained in Clinical Panel 12.2;

• as part of a generalized peripheral neuropathy.

Clinical Panel 12.1 Peripheral neuropathies

Peripheral neuropathies are amenable to several classifications, each with its own relevance:

• Histological classification is touched upon in the figure, where neuropathy originates in myelin sheaths of the top two nerve fibers and in the axon of the other three.

• Anatomical classification identifies nerve numbers and locations. Numbers include mononeuropathy, referring to a single spinal or cranial nerve (e.g. sciatica, trigeminal neuralgia, isolated peripheral nerve trauma); mononeuropathy multiplex, referring to more than one affected nerve trunk (e.g. right median and radial, left sural, right peroneal). Locational labels include plexopathy, referring to involvement of the cervical or the brachial or the lumbosacral plexus in an individual case), and radiculopathy, referring to nerve root pathology, most frequently caused by compression of a nerve root in the region of an intervertebral foramen.

The terms primary and secondary are also anatomical. A primary neuropathy originates within nerve tissue (disease of myelin sheaths or of axons). A secondary neuropathy typically is caused by anterior horn cell disease leading to axonal degeneration followed by collapse of myelin sheaths.

• Etiological classification identifies causative agencies. Headings include toxins, including lead and arsenic; immune disorders, including effects of viruses; metabolic disorders, including diabetes; vitamin deficiencies such as B₁₂ in pernicious anemia or thiamine deficiency associated with alcoholism mainly of the B series; genetic disorders such as Charcot–Marie–Tooth disease.

• Time course classification may be condensed into acute/subacute, where the patient seeks help within days/weeks of onset, and chronic, where the patient may persevere for more than a year before seeking help.

One kind of acute polyneuropathy and two kinds of chronic polyneuropathy will now be described.

Guillain–Barré syndrome (GBS) is an acute, autoimmune, inflammatory neuropathy occurring in all countries and affecting individuals aged between 8 and 80. Possibly relevant antecedent events may include a mild viral infection or immunization, or a surgical procedure. GBS is sometimes referred to as Landry’s acute ascending paralysis:. Typical presentation is a predominantly motor peripheral failure involving both somatic and autonomic nerves, commencing in the feet and hands and ascending to involve the muscles of the trunk, neck and face.

Rarely, progress may be so rapid as to cause death within a few days from respiratory and/or circulatory collapse. Usually, the acute phase lasts 1–2 weeks with motor weakness associated with diminution or loss of tendon reflexes. Electrodiagnostic examination may reveal reduced conduction velocity in motor nerves. Aching pain and tenderness occur in affected muscles along with minimal cutaneous sensory loss. Reduced autonomic function may be demonstrated by fluctuating heart rate and blood pressure and/or retention of urine requiring catherization for a few days.

Rapid recovery may be spontaneous in relatively mild cases, but many patients require either immune globulin injections or plasma exchange where this is available and safe. Where axons have degenerated in the acute phase, recovery may take more than a year and may be incomplete.

Chronic polyneuropathy originating in myelin sheaths

This type of neuropathy is associated with chronic vitamin deficiency, longstanding diabetes or chronic hypothyroidism. The myelin sheaths of the peripheral nerves degenerate while the axons remain relatively intact. Because potassium channels are largely obliterated when the sheaths are initially laid down, and because saltatory conduction is lost along with the sheaths, sensory conduction is progressively impaired. As might be anticipated, the longest nerves are the most affected, yielding ‘glove and stocking’ paresthesia (Figure CP 12.1.2). (The term paresthesia refers to sensations of numbness, pins-and-needles and/or tingling.)

Initially, demyelination may be segmental/focal as shown in Figure CP 12.1.1.

After several months, motor weakness and wasting may become evident in the muscles of the hands and feet. With further progression, joint sense and vibration sense may be lost there. (Joint sense refers to the ability to detect passive movement at a joint performed by a clinician; vibration sense refers to the ability to feel the buzz of a tuning fork applied to bone; see Ch. 16.)

Chronic polyneuropathy originating in axons

The most prevalent form of chronic polyneuropathy is one that occurs in late middle age and is of unknown causation; hence the terms idiopathic (‘private pathology’) and cryptogenic (‘hidden origin’) applied to this condition. Biopsy studies have demonstrated that the initial pathology is axonal, in the form of a distal-to-proximal dying back process, notably of small axons. In contrast to demyelinating neuropathies, the leading symptom here is chronic pain in the feet, sometimes later in the hands also. The pain is attributed to abnormal firing patterns in axons during the breakdown period and is associated with reduced conduction rates and smaller spike amplitudes. At the same time, there is reduced sensitivity to pinprick. Peripheral motor weakness may set in gradually but is seldom debilitating.

References

Pascuzzi RM. Peripheral neuropathy. Med Clin N Am. 2009;93:317-342.

Van Doorn PA, Ruts L, Jacobs BC. Clinical features, pathogenesis, and treatment of Guillain-Barré syndrome. Lancet Neurol. 2008;7:939-950.

Figure CP 12.1.1 Histological changes associated with some types of peripheral neuropathy. The figure does not distinguish between sensory and motor nerves. (A) In segmental/focal demyelination, impulse conduction is slowed or blocked but in a nerve conduction study this will not be apparent if stimulator and recorder are both placed distal to the lesion site. (B) Generalized demyelination results in conduction slowing or block although the axons may be preserved. (C) Damage to the axon causes the entire distal length of axon to break up into droplets, and the release of tension causes the myelin sheaths to follow suit (Wallerian degeneration). (D) In dying-back neuropathy, myelin breakdown is again secondary to axonal degeneration.

Figure CP 12.1.2 ‘Glove and stocking’ paresthesia.

Clinical Panel 12.2 Entrapment neuropathies

Peripheral nerves may be ‘trapped’ beneath ligamentous bridges or stretched at bony angulations, with consequent symptoms depending upon the distribution of the affected nerves. Sensory disturbances caused by compression tend to be early and prominent, motor weakness later and at times severe.

Nerve conduction studies can be helpful in defining the nerve or nerves involved, extent of damage already done, ‘monitoring’ for progression and perhaps most importantly, confirming the clinical diagnosis. Because entrapment syndromes are more frequent in the presence of generalized polyneuropathies this may be the most frequent predisposing condition to their development.

Upper limb

The most common entrapment neuropathy results from compression of the median nerve in the space between the overlying flexor retinaculum and the underlying flexor tendons within their common synovial sheath or carpal tunnel syndrome. Characteristic sensory symptoms are paresthesias in the affected hand and fingers, and bouts of pain which may extend from the hand up along the arm. These symptoms commonly occur during the night; by day they are especially brought on by grasping or pinching actions in the workplace. Wringing (flicking) the affected hand may afford some relief. On examination, the skin overlying the distal phalanges that is supplied by the median nerve, namely those of thumb, index and middle finger, show reduced sensory acuity. The thenar eminence may appear flattened due to wasting of the abductor pollicis brevis, and that muscle may be weak, in response to forward (not outward) movement of the thumb against resistance. Tapping over the nerve at the wrist may elicit paresthesias in the hand (Tinel’s sign), but this is only significant if light tapping elicits this symptom.

Cervical spondylosis, described in Chapter 14, is a potential source of confusion. This disorder is another example of ’nerve entrapment’, being caused by compression of one or more cervical spinal nerves by bony outgrowths next to apophyseal facet joints in the neck. Most commonly affected nerves are C6 (sensory to skin of lateral forearm, lateral hand and entire thumb) and C7 (sensory to skin of outer three fingers front and back). Arm and forearm tendon reflexes may be diminished and some motor weakness may be apparent in the distribution of the affected ventral roots. In addition to the more extensive cutaneous symptoms and signs, cervical spondylosis is unrelated to manual activities, seldom causes nocturnal symptoms and has a relatively advanced age profile.

Confirmatory of carpal tunnel syndrome is a prolonged distal latency in the motor nerve conduction test (Figure 12.4) and/or in the sensory nerve conduction test (Figure 12.5).

Ulnar nerve entrapment may occur at the elbow or at the wrist. At the elbow it may be compressed against the ulna by the fibrous arch linking the humeral and ulnar origins of the flexor carpi ulnaris muscle. The patient may be aware of having a sensitive ‘funny bone’ in the affected area, and/or paresthesia affecting the medial two fingers and the hypothenar skin area. In chronic cases there may be weakness of flexor carpi ulnaris and of the flexor digitorum profundus contribution to the medial two fingers. Usually, the motor weakness is confined to the hand, and this may create diagnostic confusion because compression at the wrist can have the same effect. Wrist level compression occurs in the interval between the pisiform bone and the hook of the hamate. The sensory effects are confined to the inner two fingers because the palmar branch of the nerve arises in the forearm and is spared. If only the superficial terminal motor branch to the hypothenar muscles is involved, weakness will be evident during abduction of the little finger against resistance. Involvement of the deep branch leads to weakness of abduction and adduction of index, middle and ring fingers.

Lower limb

Meralgia paresthetica (’thigh-pain with pins-and-needles’) is a condition affecting the lateral cutaneous nerve of the thigh where it pierces the inguinal ligament close to the anterior superior iliac spine. The nerve may be pinched by tension of the ligament during extended periods of exercise, e.g. playing football. It is also associated with pregnancy, where increased tissue fluid may generate a carpal tunnel syndrome at the same time. Intermittent ‘flicks’ of pins and needles are experienced on the outside of the thigh, and skin sensitivity may be progressively reduced by degeneration of the nerve. Nerve conduction from the skin of the lower lateral thigh is retarded on the affected side, as revealed by sensory evoked potentials, i.e. stimulating the skin while recording electrical activity over the contralateral somatosensory cortex. However, this procedure is rarely attempted in currently symptomatic individuals.

Sensory evoked potential techniques are described in Chapter 31.

Common peroneal nerve entrapment is a term used when the common peroneal nerve exhibits signs of compression at the level of the neck of the fibula. Here the nerve passes through a tendinous arch formed by the peroneus longus. Rarely is it a true entrapment, however. Usually the problem is one of frequent compression either during sleep or from habitual sitting with the legs crossed, whereby the nerve is pressed against the lateral condyle of the femur of the other knee. Reduced nerve conduction affecting the superficial peroneal branch leads to weakness of eversion of the foot and sensory loss in the skin of lower leg and dorsum of foot. Affecting the deep peroneal branch, it leads to weakness of dorsiflexion of the foot and toes, resulting in foot drop with characteristic slapping gait. Either branch may escape more or less completely; identification of individual affected muscles requires needle electromyography.

Iatrogenic entrapment is a well-known danger associated with application of a plaster cast following fracture of the tibia. The normal procedure is to insert protective padding before the plaster has hardened.

Tarsal tunnel syndrome results from compression of the tibial nerve and/or its plantar branches within the tarsal tunnel roofed by the flexor retinaculum of the ankle. The compression is often not from the retinaculum itself but from an outside agency such as ill-fitting footwear or a tight plaster cast following fracture of the tibia. The result is pain in the ankle region and paresthesias in the sole of the foot.

Finally, paresthesias confined to the forefoot and two or three adjacent toes are likely to be caused by squeezing of planter digital nerves between adjacent metacarpal heads

References

Shapiro BE, Preston DC. Entrapment and compressive neuropathies. Med Clin N Am. 2009;93:285-315.

Tsao B. The electrodiagnosis of cervical and lumosacral neuropathy. Neurol Clin. 2007;25:473-494.

The H response (see Ch. 12 tutorial onsite)

Owing to their deep location, nerve conduction in spinal nerve roots can only be assessed indirectly, by activating sensorimotor reflex arcs at appropriate levels. The standard test, named after Hoffmann who first described it, is known as the H response or H wave test. This is frequently used to assess overall conduction velocity in the S1 reflex arc – the same neurons that are evaluated clinically by the Achilles reflex (Figure 12.8). The tibial nerve is stimulated using the minimum current sufficient to elicit a muscle twitch. The objective here is to excite the largest myelinated afferent fibers, namely those serving annulospiral nerve endings in neuromuscular spindles, thereby eliciting a monosynaptic, minimal latency twitch in the triceps surae (gastrocnemius/soleus). The minimal latency is in fact quite long – up to 35 ms depending on the patient’s overall height – because S1 segment of the spinal cord lies behind the body of vertebra L1, creating a 130–150 cm upandown (sic!) trip. Increasing the current reaches the point where the M wave appears (Figure 12.8D). The M wave is produced by direct orthodromic activation of the motor end plates. Antidromic conduction accounts for progressive canceling out of the action potentials descending in the efferent limb of the H reflex arc.

Figure 12.8 Anatomical background of the H and M waves. (A) The H wave is mediated by a monosynaptic reflex arc as shown. (B) Recording the S1 segment Achilles reflex arc CMAP. The stimulator overlies the tibial nerve, the recorder overlies the triceps surae muscle. Both limbs of the reflex arc are within the tibial component of the sciatic nerve. (C) Increasing the current directly activates axons supplying the muscle, yielding the short-latency M wave. (D) Note that the H wave progressively disappears as stimulus intensity increases, because of cancellation of the orthodromic motor impulses in (A) by antidromic impulses newly generated by the cathode, represented by the dashed line in (C).

In the upper limb, the nerve roots of spinal nerve C6 may be tested by stimulating the median nerve and recording from flexor carpi radialis. C7 roots may be tested by stimulating the posterior cutaneous nerve of the forearm and recording from the triceps brachii.

Electromyography

Electromyography (EMG) is a technique in which an electrode incorporated into a fine needle is inserted into a muscle in order to sample the depolarization waveforms produced by voluntary contraction. There are several components to the test; when combined with the results of nerve conduction studies (NCS), they provide valuable diagnostic information.

The test begins, like the NCS, with a clinical question, and the individual muscles chosen for EMG are based on the most probable clinical diagnosis provided by the history and physical examination. For example, if there is clinical evidence suggestive of a specific nerve injury, muscles are chosen that are supplied by that nerve. Recordings from adjacent muscles (or from the same muscle on the opposite side) during contraction would also be sampled to provide control waveforms for comparison. The results are combined with NCS to make a case for or against the provisional diagnosis.

Needle electrode

The recording electrode occupies the lumen of a fine needle (Figure 12.9). An insulation sleeve isolates the recording electrode from the barrel of the needle, which functions as a reference electrode. As in the case of nerve conduction studies, the EMG record is based on the potential difference between the recording and reference electrodes. During muscle contractions, an extracellular record is taken of the low-voltage potentials that originate from the muscle membrane depolarizations.

Figure 12.9 Structure of a conventional concentric electrode. The upper picture is a face-on view depicting the insulator separating the active (recording) electrode from the reference electrode.

The needle is passed through the skin and into the muscle in question. It is then pushed, in small increments, into various portions of the muscle and after each needle movement the effect is observed. The moving needle will generate spiky, insertional activity, known as injury potentials, caused by muscle membrane depolarizations, which cease when the electrode movement stops.

The normal electromyogram

The sensitivity settings on the machine are adjusted in order to record voluntary muscle contraction. The patient is asked to slightly contract the muscle and, as they do, irregular waveforms appear representing motor unit action potentials (MUAPs). Each of these individual waveforms represents activation of the muscle fibers that belong to an individual motor unit. While the electrode is stationary, all MUAPs that are of similar shape originate from the same individual anterior horn cell and reflect depolarization of that cell. Their shape, in normal situations, is similar to the familiar QRS of an EKG (ECG) recording, and measurements are made of their amplitude, duration and morphology. Each individual MUAP is a sample of the summated depolarizations of the fibers of a single motor unit. We must bear in mind that the electrode can only record from the muscle fibers which are the closest – not all fibers of a unit contribute to the observed response. As indicated in Figure 12.10, overlap of the territories of individual anterior horn cells permits several motor units to be sampled simultaneously.

Figure 12.10 Sampling motor unit action potentials. This diagram represents the overlap of six motor units. The area (green) being sampled includes parts of five units; sampling is greatest close to the recording electrode.

The recorded waveforms tell us about the form and function of the motor units, and about changes under various pathological conditions. Each depolarization of an anterior horn cell (AHC) results in a virtually synchronous depolarization of all of its target muscle fibers. The needle electrode records a summation of the individual action potentials closest to its exposed tip, to provide a MUAP. As long as the recording electrode remains stationary, the MUAP waveform will remain the same. On the monitor they ‘march across’ at a frequency that is the same as the firing rate of the neurons being sampled. The stronger the voluntary muscle contraction, the greater the number of motor neurons recruited by the corticospinal tract and the more frequent the firing rate (Figure 12.11).

Figure 12.11 Motor unit activation at increasing strengths of voluntary contraction. (A) In this example, during weak contraction the recorder has picked up activity in two motor units, each with its characteristic shape. (B) Stronger contraction has recruited a third motor unit within reach of the electrode. (C) Substantially greater contraction has produced so much overlap of action potentials that the individual shape tracings are distorted (‘interference pattern’).

Some clinical applications

Denervation of muscle

Skeletal muscle may become denervated as a result of:

• acute physical injury to its nerve of supply, e.g. laceration or acute crush injury;

• chronic pressure on its nerve of supply, known as entrapment, e.g. progressive squeezing of the median nerve in carpal tunnel syndrome, or of the ulnar nerve in its tunnel behind the medial epicondyle;

• death of alpha motor neurons in the anterior gray horn or cranial motor nuclei, in the course of motor neuron disease (Ch. 16);

• involvement of motor nerves in the course of an acute or chronic polyneuropathy.

Some abnormal motor unit action potentials are illustrated and explained in Clinical Panel 12.3. Clinical Panel 12.4 is an account of the autoimmune disorder known as myasthenia gravis (‘grave muscle weakness’)

Clinical Panel 12.3 Abnormal motor unit action potentials

(Myasthenia gravis is described in Clinical Panel 12.4.)

Fibrillation potentials (Figure CP 12.3.1)

Figure CP 12.3.1 Characteristic waveforms under different conditions. Resting activity: (A) Normal resting muscle is silent. (B) Fibrillation potentials: low amplitude, high frequency. Contraction: (C) High-amplitude CMAP accompanied by low-amplitude potentials. (D) Normal motor unit action potential (MUAP). (E) Reinnervation: normal plus polyphasic MUAPs. (F) Normal plus giant MUAPs. (G) Low-amplitude, mostly polyphasic MUAPs.

Fibrillation potentials are a characteristc feature of relaxed muscles in the early stages of atrophy. They represent the spontaneous, electrical discharge of individual muscle cells, and are therefore of small amplitude. They take the form of abnormally small potentials, either triphasic or positive, occurring with great regularity at up to 15 Hz. They are not clinically visible and the patient is not aware. The atrophy may be caused either by a neuropathy of any kind that results in denervation of the motor end plates in the muscle under examination, or by a primary myopathy – a degenerative change originating in the muscle fibers themselves, for example in various muscular dystrophies. Denervation supersensitivity has been invoked to account for fibrillations in both conditions. Loss of end-plate innervation is known to be associated with insertion of numerous new acetylcholine receptors into the plasma membrane of denervated muscle fibers at some distance from their end plates, sufficient to evoke small localized action potentials by the minute amount of circulating acetylcholine. In primary myopathies, the likely explanation is that of a deterioration of the muscle membrane leading to failure of propogation of action potentials originating at the end plate; this appears sufficient to signal a requirement for additional receptors.

Fasciculation potentials (Figure CP 12.3.1)

Fasciculation potentials are not infrequent among healthy individuals, being perceived as a localized ‘wriggly’ sensation in a relaxed individual muscle, usually after vigorous exercise. However, in association with motor neuron degeneration from any cause, they are indicative of spontaneous development of action potentials anywhere along the lower motor neuron pathway from anterior horn cell to muscle. They are often visible as a twitching and dimpling of the overlying skin. On the EMG record they appear as somewhat misshapen MUAPs that appear infrequently and are not under voluntary control.

Prolonged polyphasic and giant MUAPs

The term polyphasic signifies an abnormally large number of positive and negative phases. Polyphasic MUAPs signify reinnervation of motor end plates vacated by earlier degeneration of their nerve supply, followed by takeover by neighboring healthy axons. Figure 12.12 provides a basic explanation. In this figure two separate motor neurons are each represented by a single parent axon supplying three muscle fibers. Following interruption of one parent axon, its vacated nerve sheaths exert a chemotropic effect, inducing the surviving stem and/or branch axons to issue collateral sprouts which eventually reinnervate the vacated end plates. The outcome is the production of giant motor unit potentials by the enlarged motor unit.

Giant MUAPs are called ‘neuropathic’ because they signify motor neuron pathology. As mentioned in Chapter 10, they occur in the elderly as a result of ‘fall out’ of spinal motor neurons. Motor neuron disease (Ch. 16) is associated with progressive loss of spinal and cranial nerve motor neurons on a much greater scale; even the neurons that provide reinnervation are eventually lost. Radiculopathy (Ch. 14) resulting from from compression of nerve roots, and axonal polyneuropathy are other causes.

Clinical Panel 12.4 Myasthenia gravis

The acetylcholine (ACh) receptors of skeletal muscle normally undergo turnover with a half-life (50% loss rate) of 12 days. New receptors are constantly synthesized in Golgi complexes located around the nuclei of the sole plate and inserted into the sarcolemma of the junctional folds. Old receptors are removed by endocytosis and degraded by lysosomes.

In myasthenia gravis, the immune system produces antibodies to the ACh receptor. The antigen–antibody complex has a half-life of only 2 days, leading to a progressive loss of receptors and shrinkage of junctional folds (Figure CP 12.4.1).

The disease usually begins in the second ot third decade in females and in the sixth or seventh decade in males. Muscles most affected are those supplied by cranial nerves, usually in a decending sequence. The symptoms and signs are those of variable weakness, expressed by inability to maintain contractions: the eyelids tend to droop, the extrinsic ocular muscles are unable to sustain the gaze, the face tends to sag, and the jaw to need support. Chewing may be difficult and swallowing may pose a threat of fluid or food inhalation – sometimes with fatal effect. Respiratory muscle weakness may also precipitate pulmonary infection. Proximal limb muscles are affected late if at all. Patients who survive the first year are likely to improve progressively.

That the weakness is not caused by nerve paralysis is easily verified by the ability to commence a movement; all that is required is a minute’s rest beforehand.

Confirmation of the diagnosis can be obtained by means of needle electromyography. The abductor pollicis brevis is suitable although not overtly affected. Nerve conduction velocity is normal, as is ACh release, but when the nerve is stimulated at a rate of 3 per second the compound motor unit action potentials rapidly dwindle. The CMAPs return to normal amplitude following injection of either edrophonium or neostigmine, which prolong the binding time of ACh with the surviving receptors.

Anticholinesterase antibody can be detected in the blood of 80–90% of patients. The antibody originates in the thymus gland, which is usually hyperplastic and contains a lymphoid tumor in 12% of patients. Removal of the thymus (if enlarged) may be beneficial if symptoms cannot be otherwise controlled.