Clinical Neurophysiology of the Motor Unit in Infants and Children

6 Clinical Neurophysiology of the Motor Unit in Infants and Children NANCY L. KUNTZ

The motor unit (Fig. 6-1) includes the lower motor neuron, spinal roots, peripheral nerves, neuromuscular junction, and muscle. Neurophysiologic tests can elucidate the ongoing physiology of this functional unit and contribute significantly to differential diagnosis. This section of the book describes neurophysiologic techniques and their application to diagnosing and treating neuromuscular disorders in infants, children, and adolescents. This chapter briefly describes commonly used neurophysiologic techniques, reviews relevant physiology, and discusses technical issues relating to testing infants and children. Optimum understanding of the information derived from commonly used neurophysiologic tests requires an understanding of the involved physiology of generation of action potentials, volume conduction, saltatory conduction, neuromuscular transmission, and muscle contraction. In depth review of these principles is beyond the scope of this chapter, and the reader is referred to recently published comprehensive reviews.1,2 The neurophysiologic techniques described in this chapter include motor nerve conduction studies (MNCS), sensory nerve conduction studies (SNCS), F-wave latencies, H reflexes, blink reflexes, repetitive stimulation of motor nerves, and needle electromyography (EMG). All these techniques are well established and have well-accepted normative data for use with adult patients.1,3-5 Application of these techniques to infants and children was initiated several decades ago6,7 and has proved to be a critically valuable adjunct to neuromuscular diagnosis in children.8 Performing neurophysiologic testing on infants, children, 130

and adolescents requires special attention to technical issues related to small and variable size and to the unique psychosocial needs of these patients. Chapter 7, written by Dr. Matthew Pitt, explores in greater depth the developmental changes in nerve conduction and motor unit potentials throughout childhood. Virtually all the disorders of the motor unit encountered in adults also occur in infants, children, and adolescents. However, one must also be prepared to evaluate and diagnose other congenital or acquired disorders that present somewhat selectively in younger patients. Disorders such as congenital myasthenic syndromes, dysmyelinating neuropathies, congenital myopathies, congenital muscular dystrophies, and hypoplasias of various portions of the motor unit are relatively unique to children. An acquired disorder such as infantile botulism has a distinct pathophysiology that causes it to selectively present in young infants. There are several excellent references that provide overviews of technical issues as well as address these unique differential diagnoses.8-10

REVIEW OF PHYSIOLOGY Generation of Action Potentials Action potentials are an “all-or-none” response. In human muscle or nerve cells, when the resting membrane potential depolarizes by about 15 to 25 mV, a critical threshold is

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FIGURE 6–2 Saltatory Conduction.

FIGURE 6–1 Motor unit anatomy.

reached and an action potential is generated. This is an energy-dependent process. Generated action potentials cause sodium channels in the membrane to open, which gives rise to a 500-fold increase in permeability to sodium ions. Increased potassium conductance and inactivation of sodium conductance are responsible for rapid recovery of the cell membrane from depolarization.11

Volume Conduction In clinical diagnostic settings, recording electrodes are rarely placed directly on the nerve or muscle. Rather, they are placed on the surface of the extremity and the underlying, variably deep nerve or muscle generates potentials in a “volume conductor.” Current flow decreases in proportion to the square of the distance from its source. Therefore, the amount of current required for stimulation and the amplitude of evoked responses depend on the depth of the target of stimulation and source of generated action potential.

Nerve Conduction Nerve fibers of varying diameter possessing myelin sheaths of different thicknesses conduct impulses within the human peripheral nervous system. Unmyelinated nerve fibers conduct action potentials along the entire length of their cell membrane with predictably slow conduction velocity (1 to 2 m/sec). These fibers serve autonomic and some somatic pain pathways. Myelinated fibers conduct at a faster velocity due to larger fiber diameters with lower axoplasmic resistance to current flow and to saltatory

conduction. The latter refers to the rapid “jumping” of depolarization from the gap at the end of myelin produced by one Schwann cell (node of Ranvier) to the next node (Fig. 6-2). This produces conduction velocities between 20 and 60 m/sec. The largest myelinated fibers function in motor nerves and vibratory and proprioceptive sensory pathways.

Physiology of Nerve Injury Neuropraxia describes a type of nerve injury in which there is a proportionate decrease in amplitude (conduction block) with stimulation proximal to the site of a lesion (Fig. 6-3). This is a physiologic or functional loss of conduction without structural injury to the axon. With another type of injury involving transection of the axon, stimuli applied distal to the site of the lesion continue to be conducted for up to 5 to 7 days, after which wallerian degeneration disrupts function. Axonotmesis refers to disruption of continuity of axons with immediate failure of conduction across the lesion and subsequent wallerian degeneration of the portion of axon disconnected from its cell body. Neuronotmesis describes a situation in which the nerve injury causes discontinuity of both axon and associated connective tissue structures. Physiologic studies cannot differentiate this from axonotmesis. However, the prognosis for nerve regeneration is poorer with neuronotmesis due to a higher incidence of failed or misdirected axonal regrowth. Nerve conduction studies (NCS) performed a week after nerve injury can differentiate axonal loss from conduction block. In the case of a complete brachial plexus lesion that has been present since birth, NCS performed at 5 to 10 days of age have prognostic value. Nerve stimulation distal to the spinal root or plexus site of injury produces preserved amplitude of motor response with neuropraxia but produces proportionately decreased amplitudes with

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FIGURE 6–3 Conduction Block.

axonal degeneration. These data provide important physiologic and prognostic information to practitioner and family.

Neuromuscular Transmission Action potentials reach the nerve terminals of motor nerves and activate a physiologic cascade of events that carries the impulse across the synaptic cleft and generates an action potential in muscle fibers if stimulation threshold is reached (Fig. 6-4). The physiology of this process is

discussed in more detail in Chapter 25. Clinical neurophysiologic techniques including repetitive stimulation of motor nerves, standard needle electromyography, and single-fiber electromyography can be used to assess neuromuscular transmission in infants and children. Maturational issues regarding neuromuscular transmission are discussed in Chapter 7.

Muscle Contraction Contraction of muscle fibers begins when action potentials cause calcium to be released into the sarcoplasmic reticulum and transverse tubules. This disinhibits troponin and leads to unmasking of active binding sites by tropomyosin. At this point, development of cross-bridges between actin and myosin filaments generates contraction of the fiber. Force is generated by the summated contraction of multiple muscle fibers pulling against the point of tendinous insertion into bone. Motor unit potentials recorded during needle electromyography are the electrical summation of activation of all the muscle fibers innervated by a single motor neuron that are within the reach of a recording probe.

DEVELOPMENTAL CONSIDERATIONS IN NEUROPHYSIOLOGIC EXAMINATION Cooperation and Tolerance for Testing FIGURE 6–4 Neuromuscular Junction. ACh, acetylcholine; CoA, coenzyme A.

Most clinical neurophysiologic techniques evaluating the motor unit include stimuli that can be described as

Clinical Neurophysiology of the Motor Unit in Infants and Children

annoying, mildly painful, or frightening. In fact, a survey of physicians performing neurophysiologic testing of the motor unit on infants and children was conducted with respondents reporting that 35% of children undergoing study experienced extreme behavioral distress (screaming, needing additional restraint, or attempting to leave the examining table).12 The electromyographer needs to consider the developmental status of the patient and, with those issues in mind, work with the family to coordinate the examination from pretest information and consent through the completion of the study. The primary decision is whether the study should be performed under sedation or carefully orchestrated in a nonsedated child. In an older child, it is also reasonable to perform the examination in multiple, shorter sessions organized to minimize discomfort and development of anxiety toward future testing. The most important factors to be considered during this decision are the probability of completing a nonsedated examination without unacceptable emotional trauma to the child and consideration of the potential medical risks of sedation in a given child. Hays, in 1992, correlated behavioral distress during electrodiagnostic procedures with a younger age, a history of being uncooperative with previous painful procedures, having had previous negative medical or dental experiences, or having parents who reported greater fear and anxiety about undergoing EMG or NCS. Potential medical risks of sedation relate primarily to underlying medical status with hypotonia or underlying cardiopulmonary disease increasing the risk of airway collapse or respiratory depression. Sedation for outpatient procedures cannot be performed as informally as in years past. Joint Commission on the Accreditation of Healthcare Organizations regulations require written procedures and monitoring by licensed personnel until effects of sedation are documented to have worn off. Heightened attention to safety concerns has transformed conscious sedation for outpatient medical procedures from a casual procedure using less than a dollar’s worth of medication administered by laboratory personnel to a formal protocol with charges of several hundred dollars. Children who can be successfully studied without sedation tend to be very young infants as well as older children and young adults. Newborn and very young infants can sleep through NCS if the stimulation is administered slowly—allowing 10 to 60 seconds rather than a fraction of a second between stimuli. With careful attention to the system and preparation for the examination, older children or young adults can tolerate these studies without sedation. The family and the patient (if he or she is old enough) need to be provided with information about the proposed study. However, the referring physician has the opportunity to play an important role in the success of the study by carefully phrasing his or her description of the study.

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Graphic descriptions of shocks and needles provided for the sake of informed consent tend to become magnified into nightmares over the days or weeks between referral and testing. A simple explanation provided by the referring physician for the parent or older child is preferable. It is much more reassuring to compare the shock to being similar to what one experiences with a simple static discharge in the winter months. Similarly when discussing the use of needles to the parent these are best compared with the size of an acupuncture tool. If the parents have continued concerns prior to the EMG they should be encouraged to speak with the electromyographer per se to lessen their anxieties. We instruct our laboratory appointment team to feel free to tell the parent we will be pleased to personally speak with them prior to the study. This often adds greatly to the rapport at the time of the procedure. Later at the time of the procedure, it is important for the performing electromyographer to provide a detailed discussion to the parent and older child. He or she should carefully explain the two primary techniques before the EMG is performed. Finally, it is most important to assure the parents that they will have control over continuation of the examination. Parenthetically, however, some electromyographers find that on some occasions the parents may wish to continue the study when the physician feels it is best to discontinue and have the child return to have the procedure under conscious sedation as described later. It is reasonable to consider providing special instruction in visualization techniques, guided imagery, and/or self-hypnosis for appropriate older children. A calm manner and positive approach by the electromyographer produce much greater tolerance of the procedure by the patient and parent. Assuring the parents that the physician is empathetic and often has children of his or her own is also reassuring. Since 1998, a significant number of infants and children have had NCS and EMG performed under conscious sedation in a cooperative effort by the Mayo Clinic Clinical Electromyography Laboratory and pediatric anesthesiologists. Oral midazolam for sedation, and a topical mixture of prilocaine and lidocaine creams to prepare the intravenous site, are administered while the child is with parents in the waiting room, prior to entering the outpatient surgery room. Additional medication, including inhaled nitrous oxide and/ or intravenous midazolam, propofol, or ketamine, are used to provide necessary sedation and amnesia. Fentanyl is also frequently used to provide analgesia. Patient and family satisfaction has been very high. The only observed side effect has been a small number of markedly weak or hypotonic infants or young children who developed transient atelectasis after sedation and required more prolonged observation. These sedative medications have little effect on

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peripheral NCS. However, central conduction may be altered by these medications, with the effect more marked at cortical than subcortical levels. F-wave responses are suppressed proportionate to the degree of clinical sedation. Clinical experience suggests that propofol suppresses the frequency of F-wave responses more than other agents used for conscious sedation.

Size Issues Infants and young children have shorter extremities, proportionately thicker subcutaneous fat layers, and greater surface areas than older children. The short extremities and small hands and feet make electrode separation more difficult and increase potential for artifact owing to spread of the electrical stimulus. Also, short distances magnify the effect of small errors in measurement. For example, in an 8-month-old infant, a measurement error of only 2 mm creates a 2% difference in conduction velocity, whereas a 1-cm error can create an 8% to 12% difference. Finally, the greater surface area in infants and children makes them more susceptible to cooling of extremities and slowing of nerve conduction (at 2 m/sec per degree centigrade temperature loss). Lower temperatures also affect neuromuscular transmission and the appearance of motor unit potentials. These technical issues are compounded when studies are done portably in intensive care units where electronic equipment increases likelihood of electrical interference.

Nerve Conduction Studies The procedure for NCS should be explained to the parent(s) to obtain informed consent. When appropriate, assent should be obtained from older children. As necessary, reassurances should be given regarding issues that are worrisome to children: The fact that the adhesive tape and the application of recording electrodes are not painful, that the stimulus is produced by the machine and is not electricity from a wall socket, and that it is normal for the stimulus to cause involuntary movement. Most children tolerate the NCS portion quite well when the electromyographer recognizes that the peripheral nerves of children are close to the surface and require a relatively low stimulus intensity in comparison with the adult patient. Furthermore, enlisting the interest of older children by having them watch the waveform develop on the screen as they “build mountains,” so to speak, is a useful technique. Parents, who have spent much time keeping their children away from electric sockets in the home, are quite reassured to hear that the electrical stimuli used are not the same as “electricity” or household current. It helps to emphasize that the stimulus is of short duration (demonstrated

by a click of the tongue) and that the sensation does not linger. Occasionally gaining the help of Mom or Dad is sometimes very useful, as one may perform a brief sensory NCS on them to gain their understanding of the relatively benign sensation that their child will experience with the NCS. If the patient wants more information, the stimulus can be likened to and demonstrated as the fast, sharp flick of finger against the skin of the electromyographer’s extremity. When older children or youth are awake during NCS, it is useful to warn them of the arrival of each stimulus using a cue such as a tongue click. This frequently helps children retain a sense of control during a stressful experience. Pediatric NCS are best accomplished by an experienced team consisting of an electromyographer and an EMG resident or technician. A large examination room is needed because a parent or extra personnel to monitor sedation are required in addition to standard equipment and personnel. Room lights that dim are helpful to promote patient relaxation and sedation. Extra time must be allotted for pediatric cases to allow for the slower pace and/or the administration of sedation. Pediatric cases can take nearly twice as long as a similar examination in a cooperative adult. Several features unique to infants and children create technical problems for the electromyographer. In newborn infants, a significant layer of subcutaneous baby fat provides an energy reserve to provide for future growth. For example, muscle contributes to less than 60% of the crosssectional diameter of the calf in newborn infants, whereas the proportion of muscle is greater than 80% in school-age children. Cutaneous nerves are relatively superficial; however, most major nerve trunks are contained in neurovascular bundles deep to baby fat. This requires the distance between anode and cathode to be greater than otherwise might be estimated necessary in these short limbs. Baby fat also tends to obscure palpable bony landmarks in infants and toddlers. The ease with which sensory nerves are studied in children varies. For example, sural SNCS can be technically challenging in infants with proportionately large layers of baby fat. Alternatively, medial plantar NCS are technically easier. In children younger than 10 years of age, sensory potentials can be frequently recorded at the ankle and the knee with stimulation of the medial plantar sensory fibers in the foot. This allows calculation of sensory nerve conduction velocity along a proximal segment. Increases in height and extremity length are dramatic throughout childhood. A simple rule of thumb is that length/ height and arm span double between birth and 2 years of age and double again by adulthood. Short distances between electrodes increase the potential for shock artifact due to spread of current, paste bridges, and so forth. Special stimu-

Clinical Neurophysiology of the Motor Unit in Infants and Children

lating electrodes need to be used in infants and toddlers to provide shorter and variable interelectrode distances. Factors that help alleviate shock artifact include careful cleansing of the skin prior to electrode application, careful physical separation of lead wires, prevention of paste bridges, use of the largest ground electrode possible, and use of paper or cloth towels to immobilize or manipulate the extremity. Constant current stimulators and near-nerve needle stimulating electrodes are used in some laboratories and have certain technical advantages.7,9 Two prospective studies on normal children demonstrated that nerve conduction measurements obtained in a given child were highly reproducible. In one study with infants,6 motor nerve conduction velocities performed on different days in 15 infants demonstrated a mean difference of 1.6 m/sec. In another study,13 the difference in sensory nerve conduction velocities performed on different days in several adolescent patients was less than 2 m/sec.

Needle Electromyography Infants and children frequently experience a degree of difficulty tolerating the needle examination owing both to the discomfort of the needle insertion and probing as well as to psychological issues relating to fear of mutilation, body penetration, or loss of control. Children should be considered for conscious sedation if they present with a history of poorly tolerating painful medical or dental procedures or if they are believed, on a developmental basis, to be unlikely to tolerate the examination. Parents are told that we expect the children to be partially alert and possibly object when the needle examination is started since there is some discomfort. We emphasize that no medication is being injected through the needle, so the child will not experience delayed soreness as with immunizations. When describing or discussing needle EMG, it is useful to call the needle electrode an “electrode” or “wire” and to assiduously avoid showing it to the patient. Some experienced electromyographers find that children respond well when they refer to the EMG needle as a “microphone that listens to the muscle”.14 The children are told they will feel a small pinch in the skin—“like a mosquito”—preceding the placement of the electrode in the muscle. Once the motor units are activated, the children are asked if they knew that their muscle could make such funny noises or what this response sounds like. The electromyographer may be surprised sometimes by the varied responses of children; in fact, their answer often creates a laugh, bringing some relaxation to the procedure per se. Simultaneous tape-recording of the needle EMG for later detailed assessment or quantitation is frequently useful. Positioning and repositioning the extremity (particularly with the muscle at its shortest length) can aid in attaining

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a silent background for examination of insertional or spontaneous activity. Observation of voluntarily activated motor unit potentials can be more difficult if the patient is deeply sedated. With experience, pediatric anesthesiologists can titrate the degree of conscious sedation to allow controlled amounts of spontaneous movement. In infants or children unable or unwilling to contract the muscle voluntarily, motor unit activity initiated by repeated passive movements, tactile stimulation, or activation of infantile or protective reflexes can be used. The quality of motor unit potential activation can be improved by use of analgesic medication to decrease ongoing discomfort and midazolam to create amnesia for most of the experience. As discussed earlier, infants and toddlers have a thick layer of body fat. One of the most important technical considerations is to use a needle electrode that is long enough to reach the muscle being studied. Use of standard concentric needle electrodes (37 to 42 mm in length, 26 gauge) has been most satisfactory. Experience has shown that the “child and facial” needles with a length of 20 mm are not long enough to reach limb muscles in many infants and children. Although monopolar needles are preferred by some clinicians, in my experience the minimal decrease in discomfort with insertion and manipulation of these needles is outweighed by the increase in background noise from the reference electrode in active limbs. Certain muscles are easier to study in children of different ages. Therefore, if the process is diffuse and does not need to be “mapped out,” the technically easiest muscles should be studied. Tibialis anterior, gluteus medius, iliopsoas, abductor digiti minimi, biceps brachii, and deltoid are muscles that can be immobilized and/or activated easily for study. The triceps is frequently activated voluntarily if the child’s hand is gently placed over the eyes or nasal bridge. Infants and children usually receive immunizations in the anterior thigh rather than the deltoid. For this reason, the anterior thigh muscles should generally be avoided on needle examination.

CLINICAL NEUROPHYSIOLOGIC TECHNIQUES Nerve Conduction Studies Nerve conduction studies can help differentiate among many similarly presenting disorders of the motor unit. Findings can outline the following: 1. Types of nerve fibers involved, such as motor versus sensory, large- versus small-diameter fibers 2. Pattern of involvement, such as diffuse versus focal or multifocal, proximal versus distal

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3. Type and degree of the physiologic insult, such as conduction block versus axonal injury

AU4: Pls. check cross reference

Knowledge of whether the axons have been partially or totally severed can determine the prognosis for and time course of recovery and whether surgical intervention may be useful. Nerve conduction techniques involve the application of brief, low-current, electrical square-wave pulses to peripheral nerves while recording the desired response over nerve or muscle. The amount of current used is adequate to stimulate the nerve fibers of interest (usually large myelinated motor or sensory fibers) but is subthreshold for the unmyelinated pain fibers. Therefore, the stimulus is usually described as a tapping, thumping, or stinging sensation. If motor fibers are activated, an involuntary brief contraction or twitch of the muscles innervated by those fibers distal to the site of stimulation occurs. Most commonly, tin disks can be taped or applied to the skin for both stimulation and recording. On occasion, subcutaneous needle electrodes must be employed to stimulate or record selectively from deeply placed nerves. Surface electrodes are obviously better tolerated by infants and children. The usefulness of the neurophysiologic information provided by NCSs is being increasingly demonstrated in pediatric medicine. Developmental changes in normative values for each of the techniques is discussed in detail in Chapter 7. Motor Nerve Conduction Studies MNCSs are performed by stimulating motor or mixed nerves and recording over the endplate region of a muscle innervated by those fibers. The summated electrical response of all the muscle fibers appears as the M wave, or compound muscle action potential (CMAP), whose onset latency, amplitude, and shape provide physiologic information. Stimulation at multiple points along the nerve produces CMAPs at different latencies. The difference in latency divided by the distance separating the points of stimulation calculates the conduction velocity of the fastest conducting fibers (Fig. 6-5). Any muscle whose nerve supply is superficial enough to be stimulated and whose endplate region is superficial enough and geometrically suited to producing a summated response can have motor nerve conduction recorded. Therefore, in addition to the commonly tested nerves in the forearms and legs, the phrenic nerve can be stimulated in the neck with the diaphragmatic CMAP recorded over the lower chest wall.15 Another clinical application of NCS would be early in the course of idiopathic facial nerve palsy when evaluation of the CMAP amplitude and distal latency evoked by facial nerve stimulation accurately predicts the clinical outcome.16 NCS have been used in countries with endemic outbreaks of poliomyelitis as a cost-effective, quick, and easy way to distinguish

FIGURE 6–5 Motor Nerve Conduction Study

FIGURE 6–6 Sensory Nerve Conduction Studies: ulnar sensory nerve action potentials. F, female; M, male; PL, peak latency; NCV, nerve conduction velocity.

poliomyelitis from other motor nerve disorders such as Guillain-Barré syndrome.17 Sensory Nerve Conduction Studies Sensory nerve action potentials (SNAPs) (Fig. 6-6) provide sensitive and specific information regarding the status of the peripheral sensory nerve fibers. As volume-conducted direct nerve action potentials, the amplitude of sensory potentials is low compared with motor responses, arising from the muscles per se (microvolts rather than millivolts). This makes it important to manage technical issues such as

Clinical Neurophysiology of the Motor Unit in Infants and Children TABLE 6–1 Methods of Performing Sensory Nerve Conduction Studies Stimulation Site

Recording Site

Cutaneous sensory nerve

Same cutaneous sensory nerve fibers at a distance Mixed nerve containing same cutaneous sensory fibers Cutaneous sensory nerve containing sensory fibers from mixed nerve

Mixed nerve

background noise and shock artifact. The shorter distances between stimulating and recording electrodes in infants and small children and the greater surface area in infants, which promotes extremity cooling, create potential challenges to high-quality SNCS in infants and children. SNCS are performed by stimulating and recording directly over sensory fibers. This can be accomplished in several manners as shown in Table 6-1. In the peripheral nervous system, sensory neurons are located in the dorsal root, in ganglia extrinsic to the spinal cord—the dorsal root ganglia. Therefore, disorders or injury to the spinal cord or anterior spinal roots may occur without disrupting the connection between a dorsal root ganglion and its peripheral sensory processes. As long as that connection is preserved, the peripheral sensory potentials remain intact. For example, spinal nerve root avulsion from severe trauma can be associated with significant motor and sensory deficit with a complete disconnection of spinal motor neurons from their anterior roots and central sensory processes from their dorsal root ganglion. In this circumstance, despite dense clinical sensory loss, the SNAPs remain intact—the lesion having occurred proximal to the dorsal root ganglion. SNCS are valuable diagnostically because they are both

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sensitive indicators of injury to peripheral nerves and useful in localizing disorders of the motor unit to preganglionic (proximal to dorsal root) and postganglionic (at or distal to the dorsal root ganglia). F-Wave Latencies F-wave latencies are late responses recorded over muscle and occur when retrograde conduction along motor axons stimulates anterograde impulses from a portion of the pool of anterior horn cells reached by the initial stimulus (Fig. 6-7). The F-wave latency includes conduction along the proximal portion of the motor axon that is not evaluated in standard peripheral MNCS. Because this response is an absolute latency, the value reflects both the conduction velocity as well as the distance traveled along the limb. Normal F-wave latencies cannot, therefore, be directly extrapolated from motor nerve conduction velocities but also need to account for limb length.9,18 H Reflexes H reflexes are a motor response elicited via activation of the same monosynaptic reflex arc that is responsible for the clinically activated muscle stretch reflex. They are produced by activation of sensory fibers by a stimulation that submaximally activates motor fibers. The name (H reflex) reflects that the initial recordings were made in hand muscles. H reflexes are more easily elicited in infants than in older children and adults. Advantages of recording H reflexes lie in the low stimulation intensity required to elicit them and in their ability to convey information about the proximal sensory and motor pathways. Normal values have been published for H reflexes recorded in hand and calf muscles (Fig. 6-8).19 Changes in H reflexes have been used to titrate optimum dosage of intrathecal baclofen in spastic children.20

FIGURE 6–7 F-wave Latencies: tibial nerve. SNS, sensivity or gain.

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FIGURE 6–8 H Reflex: stimulate tibial nerve and record soleus muscle.

Blink Reflexes Blink reflex study consists of early and late electrical responses recorded over bilateral orbicularis oculi muscles with low-intensity electrical stimulation of the supraorbital branch of the trigeminal nerve. This is a reflex arc with afferent impulses through the trigeminal nerve, multiple synapses in the pons, and an efferent limb through the facial nerve. Responses in term infants are less consistent and occur with longer latencies than those in adults. Normative data have been published for infants and children (Fig. 6-9).21 Repetitive Motor Nerve Stimulation Neuromuscular transmission can be tested with pairs of stimuli or with trains of stimuli (repetitive stimulation). Disease states frequently lower the safety margin of neuromuscular transmission such that repeated stimuli in quick succession are followed by failure of the postsynaptic membrane to generate an action potential. With repetitive stimulation, the amplitude and area of serially generated responses are compared. Repetitive stimulation at 2 to 3 Hz (Fig. 6-10) is used to evaluate postsynaptic disorders of neuromuscular transmission, including acquired autoimmune myasthenia gravis and most forms of congenital myasthenic syndrome. Rapid, repetitive stimulation at 20

FIGURE 6–9 Blink Reflex: stimulate right supraorbital nerve.

to 50 Hz (Fig. 6-11) is needed to test for the facilitation or increment in amplitude characteristic of infantile botulism and other presynaptic disorders of neuromuscular transmission. Rapid, repetitive motor nerve stimulation is uncomfortable and can be technically difficult to perform in infants and children because voluntary movement of the extremity produces artifact. Normal infants younger than 6 months of age can demonstrate decrements in CMAP amplitude

FIGURE 6–10 Slow Repetitive Stimulation: stimulate spinal accessory nerve and record trapezius muscle.

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FIGURE 6–12 Electrodes for Needle Electromyography: concentric needle/monopolar.

EMG FIGURE 6–11 Rapid Repetitive Stimulation. LES, Lambert Eaton syndrome; stimulate femoral nerve, record rectus femoris muscle.

of up to 50% in response to 20- to 50-Hz repetitive stimulation.22 Repetitive stimulation has been useful in differentiating the pathophysiologic causes of prolonged respiratory paralysis following critical illness in children. For example, polyneuropathy of critical illness and persistent neuromuscular blockade secondary to prolonged pharmacologic neuromuscular blockade can be differentiated by NCS including repetitive stimulation.23 More detailed descriptions of applying these techniques to neuromuscular disorders common to infants and children are contained in Chapter 27. Motor Unit Number Estimation Motor unit number estimation is a neurophysiologic method to estimate the number of motor units (and, therefore, lower motor neurons) innervating a specific muscle. There are several different techniques (all-or-none incremental, spike-triggered averaging, and the statistical method) that have been developed to obtain such estimates, and these are not reviewed in detail here.24,25 The multiple-point stimulation technique is based on electrical activation of single motor axons in an all-or-none fashion. A sample of single motor unit potentials can be obtained by moving the stimulating electrode to multiple points along a nerve. Motor unit number estimation values are calculated from the ratio of the maximal CMAP to the average single motor unit potential. This technique can be applied easily to the ulnar nerve–hypothenar muscle group in infants and young children with reproducible results. A modified multiple-point stimulation technique for monitoring the loss of motor neurons in infants and young children with spinal muscular atrophy has shown promise in documenting the natural course of disease progression in these patients.26

Needle Electromyography Needle electromyography is the technique most frequently used to provide qualitative and quantitative descriptions of voluntary motor units. Standard EMG is performed with a specialized recording electrode with a thickness equivalent to a 26-gauge needle and a length adequate to reach the muscle (Fig. 6-12). The electrode is inserted into a muscle, pausing at a number of sites for evaluation of the electrical response to needle insertion. Spontaneously occurring electrical activity is noted. Concomitantly, one needs to assess the voluntarily activated motor unit potentials. However, in contrast with the adolescent and the adult patient, one needs to examine the motor unit potentials when they are activated, often involuntarily, in the infant and toddler. One attempts to observe both the recruitment pattern and details of individual motor unit potentials (amplitude, duration, number of phases, stability over time). As discussed later, there are a number of different methods to quantitate the character of voluntary motor unit potentials; however, an audiovisual semiqualitative assessment is most frequently used. Standard needle EMG can reliably differentiate neurogenic processes from other motor problems in infants and children. Needle EMG can provide important information about the pathophysiology of the disease process—for example, the presence or absence of ongoing reinnervation. Most muscles in the body can be studied by EMG. The muscles that are most superficial and distinct from vascular structures and other muscles are the most easily studied. However, hooked-wire electrodes have been inserted into posterior cricoarytenoid and thyroarytenoid muscles to differentiate between vocal cord fixation and paralysis27,28 and into the diaphragm for evaluation of that muscle. Surface EMG recordings of diaphragm and intercostal muscles have been shown to correlate with the forced expiratory volume in one second in children with asthma.29 Cranial nerve-innervated muscles can be monitored by intramuscular wire electrodes as part of intraoperative monitoring.

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For example, EMG activity in lateral rectus and facial muscles during resection of fourth ventricular tumors was shown to correlate with postoperative facial weakness.30 The more complete and specific the differential diagnosis and physiologic questions to be answered, the better able the electromyographer is to select and prioritize the muscles to be studied. If a muscle biopsy is planned, the electromyographer should be informed so that that particular muscle will not be examined because needle insertion can produce artifacts difficult to differentiate from pathologic change. Patients with bleeding tendencies should be evaluated individually with consideration given to the magnitude of the clotting disorder as well as the location of the muscles to be examined. Examination of superficial muscles can usually be safely performed in patients with mild clotting problems. The findings on needle examination are somewhat different in infants and children than in adults. Frequent motor endplate regions are encountered, especially in children younger than 1 year of age or with significant central nervous system immaturity.31 Initially positive, lowamplitude, short-duration “preinnervation infantile activity” has been described in premature infants and in children with developmental disorders such as myelomeningocele when innervation has not naturally occurred.32 There is no evidence that typical fibrillation potentials occur in fullterm or older infants unless there is an abnormality in the peripheral nervous system. The time frame for appearance of positive sharp waves and fibrillation potentials as EMG evidence of denervation may well be shorter in infants than in adults. In adults, extremity muscles frequently do not demonstrate denervation for up to 21 days after spinal root injury. Fibrillation potentials may appear after a shorter interval after denervation in infants and young children. A well-documented case report of a 4030-gm infant delivered vaginally with clinical shoulder dystocia and subsequent flaccid, areflexic paralysis of the right arm demonstrated increased insertional activity with continuous runs of positive sharp waves in right shoulder and proximal forearm muscles during the first EMG on the fourth day of life. Similar changes were seen in right hand muscles on the fifth day but had not been present on the fourth day. Although an intrauterine injury was not completely excluded, the root avulsion seen on a magnetic resonance imaging study, the pattern of soft tissue injury, and the clinical history were strongly suggestive of an intrapartum insult.33 Motor unit potential recruitment does not differ significantly between children and adults. To obtain maximum information from needle EMG, it is important to characterize motor unit potential recruitment separately from evaluation of individual motor unit potential size. This is even more critical in infants and young children, in whom

congenital malformations (such as hypoplasia of muscle) can produce findings not commonly seen in adults. During standard needle EMG, judgments about motor unit potential characteristics are made by visually estimating measurements on 20 to 40 motor unit potentials individually isolated during mild to moderate contractions. The motor unit potentials recorded during standard needle EMG represent a summation of the potentials from individual muscle fibers that are innervated by a single anterior horn cell and that are within several millimeters of the recording electrode (Fig. 6-13).34 The exact number of fibers that contribute to a motor unit potential depends on the characteristics of the recording electrode (the pickup area) and its relationship to the patchy distribution of individual fibers in a given motor unit. Motor unit potentials in infants and young children are characterized by simpler configuration, shorter duration, and lower amplitude.35 In premature infants, motor unit potentials are described as monophasic or biphasic, less than 100 μV in amplitude and 1 to 4 milliseconds in duration.36 Shorter duration motor unit potentials are seen in all muscles in infants.37 The rate at which duration increases with age varies between muscles. At 20 weeks’ gestation, the range of muscle fiber diameter is 5 to 12 μm. This increases to 7 to 12 μm in fullterm infants. The muscle fiber diameter increases slowly until it reaches the adult range of 45 to 64 μm by 12 years of age. Concomitantly, the width of the endplate zone increases. In the biceps, this distance is 6 mm in fullterm infants and increases to 25 mm in adults. The increasing muscle fiber diameter means that there is more spatial dispersion of the different fibers whose action potentials summate to form the motor unit potential.

FIGURE 6–13 Contribution to Motor Unit Potential Recordings with Concentric Needle Electrode.

Clinical Neurophysiology of the Motor Unit in Infants and Children

Willison and Smythe have described a method of motor unit potential quantitation that produces a mean ratio of amplitude per turns per second.38 Further quantitative refinement has been proposed for turns analysis of the EMG interference pattern. These include “upper centile amplitude” (which defines the upper limit of the maximum peak-to-peak amplitude of the motor unit action potentials) and “number of small segments” (which is a reflection of the polyphasicity of the component motor unit action potentials).39 These techniques have evolved into development of “clouds” of turns and amplitude measurements on 500-millisecond epochs of interference pattern that vary with the force of voluntary contraction.40 This and other methods of motor unit quantitation, including motor unit number estimation, remain to be standardized in infants and children. However, individual motor unit potential characteristics in infants are different from those in adults. In infants, motor unit potentials are simpler in configuration, shorter in duration (≈ 70% adult values), and lower in amplitude (≈ 20% to 50% of adult values).35 Motor unit potential changes with aging are therefore greater with respect to amplitude (a twofold to fivefold increase) as compared to duration (an increase of only one third). Quantitative methods increase the sensitivity to minor degrees of abnormality. These may vary from manual graphic measurements to computer-generated measurements of individual motor units to theoretically derived computer programs for quantitating motor units or motor unit populations from partial interference patterns (a more moderate contraction with multiple motor units firing simultaneously).41 The latter methods are appealing for potential application to pediatric patients because they require less voluntary cooperation and are increasingly available as part of commercial

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EMG systems. Surface electrode recordings of interference patterns (motor unit potentials produced by a strong enough voluntary contraction to make it difficult to isolate individual potentials) have been studied quantitatively (mean ratio of amplitude per turns per second) in babies and young children.38 Reports of extensive experience with quantitative EMG methods in infants and children have not yet been published. Serum muscle enzymes should be drawn before needle EMG because the repeated needle insertions involved in most studies can produce a transient elevation of muscle enzymes that may confound the diagnostic effort. Disease processes that primarily involve abnormalities of the contractile mechanism of the muscle fiber tend to cause milder changes in the characteristics of the individual motor unit potentials: a tendency toward lower amplitude, briefer duration, and increased percentage of polyphasic motor unit potentials (Fig. 6-14). There is a change in motor unit potential recruitment proportional to the degree of reduced-strength–recruitment of greater numbers of motor unit potentials firing more rapidly and producing relatively less strength of contraction—but this cannot be quantified with standard EMG laboratory equipment. Therefore, it is understandable that NCS and EMG results produced changes characteristic of a myopathy in only 10% to 40% of biopsy-proven myopathies.42,43 Motor unit potentials and recruitment patterns can be difficult to differentiate from normal in some myopathic processes, including carrier states or subclinical phases of muscular dystrophies and congenital structurally distinct myopathies. Further discussion of neurophysiologic changes noted in myopathic processes is noted in Chapter 26. Disease processes that involve loss of innervation to the muscle fibers are initially characterized by decreased numbers of motor unit potentials that can be voluntarily

FIGURE 6–14 Congenital Myotonic Dystrophy: low amplitude, polyphasic motor unit potentials.

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FIGURE 6–15 Congenital Myotonic Dystrophy: fibrillation potentials.

recruited. If the denervation persists, fibrillation potentials occur spontaneously and signal the presence of denervated muscle fibers (Fig. 6-15). As reinnervation occurs, there are usually fewer but larger (higher amplitude, longer duration) motor unit potentials (Fig. 6-16). Many disease states involve variable degrees of both muscle fiber involvement and nerve fiber loss. In such cases, the concept of “myopathic” and “neurogenic” motor unit potentials is too simplistic and can be misleading. Characterization of distinct motor unit populations is useful in understanding the pathophysiology of the disease process. For example, a population of lowamplitude, polyphasic-varying motor unit potentials with decreased recruitment suggests a chronic neurogenic process with a component of ongoing reinnervation.

Single-Fiber EMG Single-fiber EMG (Fig. 6-17) is a technique that selectively records from a single or pair of muscle fibers from the same motor unit. This technique provides physiologic information about neuromuscular transmission, which can be affected by primary pathologic change in the neuromuscular junction or secondarily by denervation and reinnervation. Single-fiber EMG is particularly valuable in infants and children because of the wide range of disorders of neuromuscular transmission that occur in this age group. Collated norms for single-fiber EMG jitter and fiber density have been published in older children.44 Standard singlefiber EMG requires patient cooperation and sustained control of voluntary activation of motor unit potentials. This

FIGURE 6–16 Chronic Reinnervation: decreased numbers of large motor unit potentials.

Clinical Neurophysiology of the Motor Unit in Infants and Children

FIGURE 6–17 Single-fiber electromyography.

is extremely difficult to achieve in infants or younger children. A technique using electrical stimulation of the axon to produce the motor unit potentials to record by single-fiber EMG electrode has been described.45 This technique does not require sustained voluntary contraction and, therefore, can be used in the pediatric age group. Stimulated singlefiber EMG can be performed with the infant or child under conscious sedation. This technique has been used to facilitate evaluation of infants with botulism46 and congenital myasthenic syndromes47 and to promote an improved understanding of the pathophysiology of childhood neuromuscular disorders such as Schwartz-Jampel syndrome.48

SUMMARY With careful attention to technical details and constant awareness of the continuous process of maturation, NCS and EMG are powerful diagnostic tools for evaluating infants and children. Despite the increasing array of molecular genetics tests available for diagnosing neuromuscular disorders in infants and children, NCS and EMG remain a necessary and valuable component of our pediatric neuromuscular practice.49 NCS and EMG are useful in developing differential diagnoses, establishing prognosis, and monitoring the course of disease during surgical intervention or ongoing treatment trials. NCS and EMG continue to play an important role in the diagnosis of neuromuscular disorders. These physiologic techniques are not performed in all children with neuromuscular symptoms. For example, infants and children who present with likely diagnoses of dystrophin-deficient muscular dystrophy or spinal muscular atrophy are likely to undergo initial molecular genetics testing in an attempt to establish a definitive diagnosis. However, NCS and EMG

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remain important diagnostic techniques in infants and children with less stereotyped clinical presentations (e.g., floppy infants) or unusual clinical problems such as vocal cord paralysis28 or acute poliomyelitis.17 NCS and EMG are also valuable when disorders of neuromuscular transmission or peripheral nerve are suspected or when initial molecular genetics testing is unrevealing. NCS and EMG play a particularly important diagnostic role in the evaluation of infants and children with acute onset of weakness seen in critical care settings.23,50,51 NCS and EMG delineate the physiologic changes in many disorders and can thereby give important clues about prognosis. For example, by differentiating among acute inflammatory demyelinating polyradiculopathy, acute motor and sensory axonal neuropathy, acute motor axonal neuropathy, and inexcitable nerves in clinical Guillain-Barré syndrome, the likelihood and timeline of clinical recovery can be projected.52-54 Similarly, prognosis in focal neuropathies (including facial neuropathies) can be projected from physiologic information obtained from NCS and EMG.16 Other studies have shown that CMAP amplitude and findings on needle electromyography can supplement clinical findings to develop a prognosis for infants and children presenting with spinal muscular atrophy.55 NCS, EMG, and evoked potentials are increasingly being used during surgical intervention to monitor neurophysiology and minimize morbidity. These techniques are particularly useful in monitoring posterior fossa surgery,30 spinal cord surgery, and surgical dissections of the anterior neck.56 NCSs, including repetitive stimulation, have been used in randomized clinical trials to assess effectiveness of new anesthetic agents57 and to monitor prolonged therapeutic paralysis.58 Surface EMG has been used to evaluate movement disorders in children.59 EMG-guided botulinum toxin injections are used to treat disorders of motor control.60 Surface EMG is also used as an integral component of biofeedback training in children with voiding dysfunction unresponsive to other therapies.61,62 In summary, clinical neurophysiologic techniques can be used to characterize the neurophysiology of the motor unit. Application of these techniques allows one to define disorders affecting the anterior horn cell, spinal nerve roots, peripheral nerves, nerve terminals, neuromuscular junction, and/or muscle. Technical problems relating to small size, decreased voluntary cooperation, rapid change of normal values during maturation, and less well-defined normal values make the application of these techniques in infants and children more challenging. Nevertheless, with collaboration between the referring physician, parent, patient, and electromyographer, exacting pathophysiologic information can be obtained that may not be available by any other means. The potential exists to use these techniques not only for diagnostic purposes but also for

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prognostic purposes and for following the course of disease during clinical treatment trials.

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52. Bradshaw DY, Jones HR Jr: Guillain-Barré syndrome in children: Clinical course, electrodiagnosis, and prognosis. Muscle Nerve 1992;15:500-506. 53. Phillips JP, Kincaid JC, Garg BP: Acute motor axonal neuropathy in childhood: Clinical and MRI findings. Pediatr Neurol 1997;16:152-155. 54. Massaro ME, Rodriguez EC, Pociecha J, et al: Nerve biopsy in children with severe Guillain-Barré syndrome and inexcitable motor nerves. Neurology 1998;51:394-398. 55. Kuntz NL, Gomez MR, Daube JR: Prognosis in childhood proximal spinal muscular atrophy. Neurology 1980;30:378. 56. Horn D, Rotzscher VM: Intraoperative electromyogram monitoring of the recurrent laryngeal nerve: Experience with an intralaryngeal surface electrode—a method to reduce the risk of recurrent laryngeal nerve injury during thyroid surgery. Langenbecks Arch Surg 1999;384:392-395. 57. Kenaan CA, Estacio RL, Bikhazi GB: Pharmacodynamics and intubating conditions of cisatracurium in children during halothane and opioid anesthesia. J Clin Anesth 2000;12:173-176. 58. Brandom BW, Yellon RF, Lloyd ME, et al: Recovery from doxacurium infusion administered to produce immobility for more than four days in pediatric patients in the intensive care unit. Anesth Analg 1997;84:307-314. 59. Oguro K, Kobayashi J, Aiba H, et al: Electrophysiological study of myoclonus in pediatric practice. Electromyogr Clin Neurophysiol 1998;38:207-221. 60. Heinen F, Wissel J, Philipsen A, et al: Interventional neuropediatrics: Treatment of dystonic and spastic muscular hyperactivity with botulinum toxin A. Neuropediatrics 1997;28:307-313. 61. McKenna PH, Herndon CD, Connery S, Ferrer FA: Pelvic floor muscle retraining for pediatric voiding dysfunction using interactive computer games. J Urol 1999;162:1056-1062. 62. Yamanishi T, Yasuda K, Murayama N, et al: Biofeedback training for detrusor overactivity in children. J Urol 2000;164:1686-1690.