Neuromuscular rehabilitation and electrodiagnosis. 4. Pediatric issues

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Neuromuscular Rehabilitation and Electrodiagnosis. 4. Pediatric Issues Chong-Tae Kim, MD, PhD, Jeffrey A. Strommen, MD, Jeffery S. Johns, MD, Jay M. Weiss, MD, Lyn D. Weiss, MD, Faren H. Williams, MD, MS, Ira G. Rashbaum, MD ABSTRACT. Kim C-T, Strommen JA, Johns JS, Weiss JM, Weiss LD, Williams FH, Rashbaum IG. Neuromuscular rehabilitation and electrodiagnosis. 4. Pediatric issues. Arch Phys Med Rehabil 2005;86(3 Suppl 1):S28-32. This self-directed learning module highlights the physician’s role in the diagnosis and treatment of neuromuscular disorders in pediatric populations. It is part of the chapter on neuromuscular rehabilitation and electrodiagnosis in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. This article discusses both clinical and electrodiagnostic features of common neuromuscular disorders in pediatric populations. The diagnostic value of somatosensory evoked potential is reviewed in a case of traumatic spinal cord injury without radiographic abnormality. Therapeutic interventions of progressive muscular dystrophy are discussed, as well as the differential diagnosis of floppy infant syndrome, the most common pediatric electrodiagnostic referral. Overall Article Objectives: (a) To become familiar with electrodiagnosis and rehabilitation for common neuromuscular disorders in the pediatric population, (b) to undrstand electrodiagnostic findings of Guillain-Barré syndrome corresponding to pathophysiology, (c) to become familiar with somatosensory evoked potentials, and (d) to be able to make differential diagnosis of floppy infant syndrome based on clinical findings as well as electrodiagnosis. Key Words: Electrodiagnosis; Evoked potentials, somatosensory; Muscular dystrophies; Pediatrics; Rehabilitation. © 2005 by the American Academy of Physical Medicine and Rehabilitation 4.1

Clinical Activity: To develop an electrodiagnostic plan for an 11-year-old girl with recent upper-respiratory infection who has pain and tetraparesis.

UILLAIN-BARRÉ SYNDROME (GBS), or acute inflammatory demyelinating polyradiculoneuropathy, typically G begins with abnormal sensation and is followed by ascending weakness after a viral illness, vaccination, surgery, or idiopa-

From the Division of Child Development and Rehabilitation, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA (Kim); Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN (Strommen); Department of Physical Medicine and Rehabilitation, Charlotte Institute of Rehabilitation, Charlotte, NC (Johns); Long Island PMR, Levittown, NY (JM Weiss); Department of Physical Medicine and Rehabilitation, Nassau University Medical Center, East Meadow, NY (LD Weiss); Section of Physical Medicine and Rehabilitation, Philadelphia Veterans Administration Medical Center and University of Pennsylvania, Philadelphia, PA (Williams); and Department of Rehabilitation Medicine, New York University Medical Center, New York, NY (Rashbaum). No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the author(s) or upon any organization with which the author(s) is/are associated. Reprint requests to Chong-Tae Kim, MD, PhD, Children’s Hosp of Philadelphia, Div of Child Dev & Rehab, 3405 Civic Center Blvd, Philadelphia, PA 19104, e-mail: [email protected]. 0003-9993/05/8603S-9598$30.00/0 doi:10.1016/j.apmr.2004.12.006

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thy. Pain is common in GBS, however, its diagnosis may be more difficult in children.1,2 Pediatric GBS is sometimes misdiagnosed because of associated pain. Albumin-cell dissociation of the cerebrospinal fluid is usually normal in the first 48 hours, then becomes abnormal in the second week. Therefore, electrodiagnosis is the most valuable diagnostic tool, especially in the acute phase of GBS. Although it is a demyelinating disease, both the axon and myelin can be involved, depending on the severity. The more somatic and autonomic nerves involved and the more axon and myelin involved, the worse the prognosis. Lesions develop initially at multiple root levels with perivascular and endoneurial infiltrates of lymphocytes. Distal segments are affected followed by the middle portions of the peripheral nerves. This histopathologic sequence is related to chronologic electrodiagnostic changes. In the acute phase of GBS (⬍7d postonset), late responses are characteristically abnormal (F wave, H-reflex) under normal distal conduction studies. Reportedly, H-reflex is the most sensitive test (more sensitive than F wave),3 followed by prolonged distal latencies of sensory and motor nerves. Significant temporal dispersion of the compound muscle action potentials (CMAPs) and slow conduction velocity are consistent with characteristic demyelinating lesions. Abnormal findings of the median sensory nerve are more common than those of the sural nerve.3 Finally, focal segmental conduction block follows between the proximal and distal segments. Fibrillation and/or positive sharp waves can be noted in the paralyzed muscles if the lesion advances into the axons, but it is not significantly associated with prognosis. Rather, the smaller CMAP amplitudes associate with poor prognosis. A reduced CMAP amplitude of less than 10% of the lower normative limit is a strong predictor for poor outcome.4 Otherwise, ventilator dependence and rapid evolution of neurologic deficits correlate with poor prognosis.5 Early diagnosis of GBS is important in order to start early therapy, which may result in better outcomes. Because F waves are significantly modulated by central nervous system (CNS) factors, meticulous interpretation is required. The absence of F waves in a patient with acute weakness accompanied by hyporeflexia and hypotonia does not distinguish between peripheral nerve system (PNS) and CNS lesions.6 Comprehensive sensory examination may help differentiate PNS lesions from acute CNS lesions (sensory amplitudes are decreased in peripheral lesion; they are normal in central lesion). Persistent conduction block may exist for months or years after clinical recovery. The severity of neurologic abnormality is related to the extent of conduction block rather than to the degree of slowing of conduction. Longstanding weakness can be predicted when (denervation) potentials present in the acute phase. Miller-Fisher syndrome (MFS), a variant of GBS, is characterized by ataxia, areflexia, and ophthalmoparesis, with minimal, if any, limb weakness. It is associated with the antibody to GQ1b (tetrasyalonanglioside).7,8 Nerve condition studies (NCSs) of the extremities show reduced CMAPs (⬍50% of normal) and reduced sensory nerve action potential (⬍50% of

PEDIATRIC ISSUES, Kim

normal), and motor conduction velocities are minimally slowed (⬍20% of normal). Moderately reduced facial CMAPs and abnormal blink reflexes are commonly coincident.8-10 As with GBS, late responses in MFS are abnormal. However, electrodiagnostic studies of children with MFS report conflicting results.10-12 Intravenous immunoglobulin (IVIG) administration and plasmapheresis are common treatments for acute or recurrent GBS. Earlier clinical improvement suggests a better prognosis. Despite the introduction of IVIG, in a recent study,13 23% of children with GBS showed evidence of long-term mild muscle weakness with minimal impact on function. Younger age (⬍9y) and a rapid progression during the acute GBS period have predicted long-term sequelae.13 Recurrence is seen in up to 5% of patients. The clinical course of recurrent GBS is similar to that of acute GBS and seems unresponsive to immunosuppressive therapy. Cerebrospinal analysis and electrodiagnostic findings demonstrate similar patterns to primary GBS.14 4.2

Clinical Activity: To provide an electrodiagnostic plan for a 4-year-old boy with paraplegia and normal imaging after a motor vehicle collision.

Spinal cord injury without radiographic abnormality (SCIWORA), the occurrence of a spinal cord injury despite normal plain radiographs, is due to the ligamentous flexibility and elasticity of the immature spine. The most common magnetic resonance image (MRI) findings are central disk herniation, spinal stenosis, and cord edema or contusion. SCIWORA can develop at any age and at any spinal cord level, but it develops most commonly in the cervical spinal cord of children under age 10.15-17 The reported incidence range varies, depending on the studies and definitions. Spinal MRI helps to identify the cord lesion. The incidence of MRI-negative SCIWORA has decreased to .08%.16,18 There are, however, a few reports of SCIWORA with negative-cord MRI.18-20 These findings suggested that MRI may lack the sensitivity to detect spinal cord dysfunction. It is not easy to evaluate motor or sensory function in young children, especially in the acute phase. For example, reflexic withdrawal is sometimes misinterpreted as voluntary movement. NCSs are recommended to rule out nerve injury. Somatosensory evoked potential (SSEP) or motor-evoked potential (MEP) studies are useful tools with which to assess the conductivity of sensory or motor pathways, respectively. To decrease background noise potentials from other brain areas, the patient’s cooperation is required. Young children may not tolerate these evoked potential studies. Conscious sedation with chloral hydrate or a short half-life benzodiazepine is required. Multichannel recording systems are preferred. Fourchannel recording systems are commonly used to monitor SSEPs, stimulating the right tibial nerve and recording over the sensory cortex, thoracic spine, lumbar spine, and peripheral nerves, using either surface or percutaneous needle electrodes. A common ground electrode is located between stimulation and the channel 1 electrodes. Before starting electric stimulation, one must be careful not to exceed 5000⍀ of impedance of the recording electrodes. High impedance is usually resolved with good skin preparation or solid contact between the skin and electrodes. It is important to wait several minutes until reaching balanced chemoelectrolytic reaction between electronic gel and electrolyte. The stimulation threshold should be low but sufficient to obtain a visible muscle contraction. The cathode is placed proximally and the ground electrode is placed between the stimulating and recording electrodes. Electric interference

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should be minimized. To avoid 60-Hz interference, stimulate at 3.1Hz (not as an integral of 60Hz). Between 300 and 500 stimulations are needed to increase the signal-to-noise ratio. To confirm the presence of a response, repeat the stimulation without changing the previous settings. Age and body height should be considered when interpreting peripheral nerve studies. Normative pediatric values must be used, given that central conduction is slower than in adults.21-23 The SSEP amplitudes of the peripheral regions (extremities and spine) in children are larger, but cortical potentials are smaller than in adults. Those findings correlate with CNS maturation.21,22 If the first positive response (P1) of the scalp recording shows symmetrically normal amplitudes and latency, then it is consistent with intact sensory pathways through the spinal cord. If the latencies or amplitudes are significantly asymmetric, then it is recommended that one repeat the study of the abnormal side. When both tibial nerve studies are abnormal, then a median nerve SSEP should be tested to help localize the spinal cord lesion. Because the course of the median nerve differs from that of the tibial nerve both peripherally and centrally, the recording sites differ. The right median nerve is stimulated at the wrist with recording electrodes at the antecubital fossa, Erb’s point, the C2 spinous process, and the contralateral sensory cortex. If the right median SSEP is normal but the tibial SSEP is abnormal, then there is also a sensory pathway block below the cervical level. MEPs may be indicated in certain cases, because SSEPs evaluate only sensory pathways. 4.3

Clinical Activity: To construct an electrodiagnostic and management course for a 5-year-old boy with clumsiness and unsteady gait.

Patients with Duchenne muscular dystrophy (DMD) typically present with normal development in earlier ages and then difficulty with walking and climbing from age 3 to 5 years, calf pseudohypertrophy, and progressive proximal weakness. Muscle enzymes (creatine kinase, lactate dehydrogenase, transaminases) are higher than normative ranges. Dystrophin, one of the skeletal and cardiac muscle membrane proteins, is located in the subsarcolemmal region and is rich at the myotendinous and neuromuscular junctions. Its function is not fully understood, but it is believed to contribute to stabilize muscle membrane during contraction and relaxation, and it helps with differentiation of muscle fibers into type 2 fibers.24 Patients with DMD have a significant dystrophin deficiency. It is caused by development of a frame-shift mutation or new mutation of the gene. Muscle weakness begins with proximal muscles symmetrically and continues to progress. Gower sign, forward flexion of the trunk and pushing both hands on the anterior thighs while standing from sitting position, is not specific to DMD; it is among the signs of proximal muscle weakness. By age 9 to 13, patients are unable to walk and become wheelchair dependent. The differential diagnosis for weakness in this case is 3-fold. Hereditary motor sensory neuropathy (HMSN) type II, spinal muscular atrophy type III, and inflammatory myopathy should be considered. Normal motor and sensory conduction study helps to rule out HMSN type II. Reduced amplitudes of CMAP may be seen if muscle atrophy is severe; otherwise, sensory and motor conduction studies are normal. Needle electromyography findings in DMD reveal myopathic changes consisting of abnormal spontaneous activity, early recruitment with small amplitude, and short duration, polyphasic motor unit action potentials (MUAPs). There is a controversy whether neurogenic factors are involved in MUAP changes in DMD.25,26 Arch Phys Med Rehabil Vol 86, Suppl 1, March 2005

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PEDIATRIC ISSUES, Kim Table 1: Differential Diagnosis of Floppy Infant Syndrome Feature

Group 1

Lesion

CNS multisystem

Onset Weakness Associated signs or symptoms

Since birth Moderate Upper motoneuron signs, seizure, dysmorphism

Entities

Hypoxic encephalopathy, infantile stroke, sepsis, dysgenetic syndrome, congenital hypothyroidism

Diagnostic tools

Imaging, laboratory

Electrodiagnostic findings

Nonspecific

Group 2

Group 3

Motoneuron, NMJ, muscle Since birth Severe Lower motoneuron signs, maternal factors (medications)

SMA type I, HMSN type III, congenital MG, transient myasthenic, congenital myotonic dystrophy, congenital myopathy, metabolic myopathy, poliomyelitis, maternal intoxication Electrodiagnosis, laboratory Depending on diagnosis

Group 4

Motoneuron, NMJ

CNS multisystem

2-6mo Severe Lower motoneuron signs, overall normal milestone prior to weakness development SMA type II, infantile GBS, infantile botulism, congenital myasthenic, congenital MG

2-6mo Moderate Slow progress, family history

Electrodiagnosis, laboratory Depending on diagnosis

Imaging, laboratory

Metabolic encephalopathy, endocrine-metabolic disease, essential hypotonia

Disease-specific

Abbreviations: MG, myasthenia gravis; SMA, spinal muscular atrophy.

Loss of hip extensors and ankle dorsiflexor strength are the primary predictors of loss of ambulation in DMD.27 There is a debate whether muscular training is beneficial or harmful for patients with myopathic disorders. Generally, high-resistance strength training at submaximal and possibly also at nearmaximal levels seems beneficial, at least in the short term, for slowly progressive myopathic disorders. The long-term effects of such training have not been systematically studied. In rapidly progressing myopathies, such as DMD, which are caused by deficient structural proteins, use of high-resistance training is far more questionable. If exercise regimens are to be used, they should preferably commence in the early stages of the disease, at which time there is still a substantial amount of trainable muscle fibers.28 It is controversial to use electric stimulation for patients with DMD. Researchers29,30 have found no difference in strength noted after 3 months of electric stimulation, but after 9 months of electric stimulation there was some improvement in ankle torque. A long-term retrospective study31 reported that optimal contracture management occurred with a combination of daily passive stretching exercises of heel cords and hamstrings, prescribed periods of standing and walking, Achilles’ tenotomy, posterior tibial-tendon transfer, and application of knee-anklefoot orthoses (KAFOs). This aggressive management program extended ambulation to a mean age of 13.6 years. After losing functional ambulation, the ability to stand with bracing continued for another 2 years.31 Twenty percent of DMD patients sustained fractures, usually fall related, that significantly impacted mobility. Forty-one percent of fractures were in patients between the ages of 8 and 11 years. Upper-limb fractures were most common in boys using KAFOs while lower-limb fractures predominated in wheelchair-dependent boys.32 Vital capacity less than 1L is associated with a 5-year survival rate of 8%.33 The maximal vital capacity recorded, and its rate of decline, predicted survival time. Serial spirometry is a simple and useful way to assess disease progression in DMD Arch Phys Med Rehabil Vol 86, Suppl 1, March 2005

patients and it should be considered when planning treatment trials.34,35 Pursed lip breathing and deep breathing are effective and easily employed strategies that significantly improve tidal volume and oxygen saturation in subjects with DMD. No pharmacologic agent has been proven effective in DMD; however, a glucocorticoid (deflazacort) was reported to preserve gross motor and pulmonary function with limited side effects.36 One third of patients developed asymptomatic cataracts while hypertension, glucosuria, acne, infection, or skin rash were uncommon.34 Long-term pulsed prednisone therapy may prolong ambulation and merits further investigation.37 Steroid therapy for ambulatory patients may prolong the ability to walk by 2 to 5 years.38 4.4

Clinical Activity: To determine an electrodiagnostic and treatment plan for an infant with hypotonia and generalized weakness.

Floppy infant syndrome has many causes, including disorders of the brain, spinal cord, peripheral nerve, neuromuscular junction (NMJ), muscle, ligament, or idiopathic origin. About 80% of patients with floppy infant syndrome have primary CNS lesion. Classification into 4 groups can be made by age and severity of weakness (table 1). Upper motoneuron versus lower motoneuron findings and anatomic distribution of weakness are also helpful in approaching the differential diagnosis. Motor weakness is more prominent in lower motoneuron disorders than in central or systemic processes. Maternal medical conditions, perinatal history, and family history should be obtained. Infantile spinal muscular atrophy (SMA) type I, congenital muscular dystrophy, congenital myotonic dystrophy, and neonatal myasthenia gravis (MG) are the most common causes of neonatal (birth to 1mo) floppiness.38-40 During the infantile period (1mo-1y), infantile SMA type II, infantile acute infectious neurologic disorders (GBS, meningitis, transverse myeli-

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tis), and botulism are known to be the most common causes of generalized hypotonic weakness. The most common reason for electrodiagnostic referral in the young infant is to evaluate a floppy baby. Although brain imaging studies, metabolic screening, and genetic studies play an important role for diagnosis of all 4 groups shown in table 1, both electrodiagnosis and nerve and muscle biopsies are still very vital tools,41 especially for groups 2 and 3, to help obtain a diagnosis and to formulate a therapeutic plan.42 Because early muscle biopsy can be misleading in SMA type I, the diagnosis is assessed by clinical and electrodiagnostic findings. Electrodiagnosis can confirm anterior horn cell lesions and justify the DNA study.43 Because of smaller amplitudes and shorter MUAP duration, it is technically more difficult to detect myopathic findings than neuropathic findings in infants and children.44 Pediatric electrodes and stimulators are recommended. If they are unavailable, adult electrodes may be used but may need to be trimmed. They should be of identical size to prevent technical problems. Electrodiagnosis for Group 2 Patients with SMA type I demonstrate predominantly progressive and generalized weakness (neck, trunk, and extremities) with less predominant weakness of bulbar muscles, but tongue fasciculations are pathognomonic. Needle electromyography in patients with SMA type I reveals abnormal resting potentials (fibrillations, positive sharp waves) as well as fasciculation potentials and high amplitude polyphasic MUAPs with reduced interference pattern. Complex MUAPs with satellites are noted secondary to increasing desynchronization during progressive denervation and reinnervation.45 Sensory and motor NCSs are normal. If NCSs are abnormal, peripheral nerve lesions should be considered. HMSN type III (Dejerine-Sotas syndrome) characteristically shows sensorimotor dysfunction with very slow conduction velocities with temporal dispersion but without conduction block. Those infants have a pattern of an autosomal recessive trait.46 Congenital myopathy is characterized by generalized hypotonia after birth with other congenital skeletal abnormalities such as hip dislocation, pes cavus, and delayed motor milestones, etc. However, electromyographic findings are normal in all congenital myopathies except myotubular (or centronuclear) myopathy. Myotonic discharge can be seen in patients with congenital myotonic dystrophy, but some of these patients show no evidence of clinical or electrodiagnostic myotonia until the age of 5 years or later. Thorough multiorgan system evaluation (eye, heart, gastrointestinal tract, and genitourinary tract) is recommended for these patients. Myotonia develops in infancy or early childhood, but remains mild throughout life in myotonia congenital. These children have no multiorgan involvement but have myotonia, calf hypertrophy, little loss of strength, and worsening of myotonia by cold exposure and percussion. Repetitive stimulation at low frequency reveals characteristic continuous decremental responses without leveling off, which is different from NMJ disorders (see Study Guide, Activity 3.447). Needle electromyography shows myopathic findings (see Study Guide, Activity 3.247). Neonatal transient MG is most common among the infants born to mothers with myasthenia gravis. Maternal antiacetylcholine receptor antibody (anti-AChR Ab) transmits vertically so the antibodies are usually positive. Generalized weakness, respiratory distress, and multiple joint contractures are associated, but symptoms subside progressively. Anticholinesterase (AChE) inhibitors improve the symptoms dramatically. Congenital MG is quite different from neonatal transient MG.

Deficiency of AChE results in generalized weakness, including in the respiratory and bulbar muscles. Anti-AChR Ab is negative. Doublet CMAPs can be noted by single stimulation and decremental responses at low frequency repetitive stimulation are the same as in adult onset MG. Muscle biopsy findings show type II muscle fiber atrophy with predominant type I and absent AChE staining because of endplate AChE deficiency. Electrodiagnosis for Group 3 Infantile botulism can be differentiated from SMA type II by acute onset of generalized weakness, especially after honey consumption or exposure to construction areas. Children with infantile botulism have weakness of all muscles, both skeletal and smooth. They show poor feeding, constipation, poor head and trunk control, and extremity weakness. The diagnosis is confirmed by the detection of the organism or its toxin in the infant’s stool. Antibiotics have not been shown to ameliorate the course of the disease. Aminoglycosides should be avoided because of their side effect of neuromuscular blockade. Early administration of human botulism immunoglobulin is known to modify the course of the disease. Prognosis for complete recovery is excellent. Repetitive stimulation is useful in the diagnosis of infantile botulism. A decremental response at a low rate of stimulation and incremental response at a high rate of stimulation is diagnostic. In contrast to myasthenic syndrome, infantile botulism shows no pattern of posttetanic exhaustion with repetitive stimulation. Also, diffuse myopathic needle electromyography findings are uncommon in infantile botulism. The NCS findings are generally normal in both infantile botulism and SMA type II. Needle electromyography findings of SMA type II are similar to those of SMA type I. References 1. Moulin DE, Hagen N, Feasby TE, Amireh R, Hahn A. Pain in Guillain-Barré syndrome. Neurology 1997;48:328-31. *2. Nguyen DK, Agenarioti-Belanger S, Vanasse M. Pain and the Guillain-Barré syndrome in children under 6 years old. J Pediatr 1999;134:773-6. *3. Gordon PH, Wilbourn AJ. Early electrodiagnostic findings in Guillain-Barré syndrome. Arch Neurol 2001;58:913-7. *4. Miller RG, Peterson GW, Daube JR, Albers JW. Prognostic value of electrodiagnosis in Guillain-Barré syndrome. Muscle Nerve 1988;11:769-74. 5. McKhann GM. Guillain-Barré syndrome: clinical and therapeutic observations. Ann Neurol 1990;27(Suppl):S13-6. 6. Marras C, Midroni G. Transient absence of F-waves in acute myelopathy: a potential source of diagnostic error. Electromyogr Clin Neurophysiol 2000;40:109-12. 7. Uncini A, Ligaresi A. Fisher syndrome with tetraparesis and antibody to GQ b1: evidence for motor nerve terminal block. Muscle Nerve 1999;22:640-4. 8. Ogawara K, Kuwabara S, Yuki N. Fisher syndrome or Bickerstaff brainstem encephalitis? Anti-GQ 1b IgG antibody syndrome involving both the peripheral and central nervous systems. Muscle Nerve 2002;26:845-9. *9. Fross RD, Daube JR. Neuropathy in the Miller Fisher syndrome: clinical and electrophysiologic findings. Neurology 1987;37: 1493-8. 10. Scelsa SN, Herskovitz S. Miller Fisher syndrome: axonal, demyelinating or both? Electromyogr Clin Neurophysiol 2000;40: 497-502.

*Key references.

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11. Katsuno M, Ando T, Hakusui S, Yanagi T, Sobue G. Motor conduction studies in Miller Fisher syndrome with severe tetraparesis. Muscle Nerve 2002;25:378-82. 12. Calleja J, Garcia A, de Pablos C, Polo JM. [Miller-Fisher syndrome: electrophysiological serial study of five patients] [Spanish]. Rev Neurol 1998;27:60-4. 13. Vajsar J, Fehlings D, Stephens D. Long-term outcome in children with Guillain-Barré syndrome. J Pediatr 2003;142:305-9. 14. Grand’Maison F, Feasby TE, Hahn AF, Koopman WJ. Recurrent Guillain-Barré syndrome. Clinical and laboratory features. Brain 1992;115:1093-106. 15. Brown RL, Brunn MA, Garcia VF. Cervical spine injuries in children: a review of 103 patients treated consecutively at a level 1 pediatric trauma center. J Pediatr Surg 2001;36:1107-14. *16. Hendey GW, Wolfson AB, Mower WR, Hoffman JR; National Emergency X-Radiography Utilization Study Group. Spinal cord injury without radiographic abnormality: results of the National Emergency X-Radiography Utilization Study in blunt cervical trauma. J Trauma 2002;53:1-4. 17. Yamaguchi S, Hida K, Akino M, Yano S, Saito H, Iwasaki Y. A case of pediatric thoracic SCIWORA following minor trauma. Childs Nerv Syst 2002;18:241-3. 18. Strohm PC, Jaeger M, Kostler W, Sudkamp N. [SCIWORAsyndrome: case report and review of the literature] [German]. Unfallchirurg 2003;101:82-4. 19. Grabb PA, Pang D. Magnetic resonance imaging in the evaluation of spinal cord injury without radiographic abnormality in children. Neurosurgery 1994;35:406-14. 20. Dare AO, Dias MS, Li V. Magnetic resonance imaging correlation in pediatric spinal cord injury without radiographic abnormality. J Neurosurg Spine 2002;97:33-9. *21. Boor R, Goebel B. Maturation of near-field and far-field somatosensory evoked potentials after median nerve stimulation in children under 4 years of age. Clin Neurophysiol 2000;111:107081. *22. Ferri R, Del Gracco S, Elia M, Musumeci SA. Age-related changes of cortical excitability in subjects with sleep-enhanced centrotemporal spikes: a somatosensory evoked potential study. Clin Neurophysiol 2000;111:591-9. *23. Taylor MJ, Fagan ER. SEPs to median nerve stimulation: normative data for paediatrics. Electroencephalogr Clin Neurophysiol 1988;71:323-30. 24. Gaschen F, Burgunder JM. Changes of skeletal muscle in young dystrophin-deficient cats: a morphological and morphometric study. Acta Neuropathol (Berl) 2001;101:591-600. 25. Piotrkiewicz M, Hausmanowa-Petrusewicz I, Mierzejewska J. Are motoneurons involved in muscular dystrophy? Clin Neurophysiol 1999;110:1111-22. 26. Rowinska-Marcinska K, Szmidt-Salkowska E, Kopec A, Wawro A, Karwanska A. Motor unit changes in inflammatory myopathy and progressive muscular dystrophy. Electromyogr Clin Neurophysiol 2000;40:431-9. *27. Bakker JP, De Groot IJ, Beelen A, Lankhorst GJ. Predictive factors of cessation of ambulation in patients with Duchenne muscular dystrophy. Am J Phys Med Rehabil 2002;81:906-12. 28. Ansved T. Muscle training in muscular dystrophies. Acta Physiol Scand 2001;71:359-66.

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29. Zupan A. Long-term electrical stimulation of muscles in children with Duchenne and Becker muscular dystrophy. Muscle Nerve 1992;15:362-7. *30. Zupan A, Gregoric M, Valencic V, Vandot S. Effects of electrical stimulation on muscles of children with Duchenne and Becker muscular dystrophy. Neuropediatrics 1993;24:189-92. *31. Vignos PJ, Wagner MB, Karlinchak B, Katirji B. Evaluation of a program for long-term treatment of Duchenne muscular dystrophy. Experience at the University Hospitals of Cleveland. J Bone Joint Surg Am 1996;78:1844-52. 32. McDonald DG, Kinali M, Gallagher AC, et al. Fracture prevalence in Duchenne muscular dystrophy. Dev Med Child Neurol 2002;44:695-8. 33. Phillips MF, Quinlivan RC, Edwards RH, Calverley PM. Changes in spirometry over time as a prognostic marker in patients with Duchenne muscular dystrophy. Am J Respir Crit Care Med 2001;164:2191-4. *34. Phillip MF, Quinlivan RC, Edwards RH, Calverley PM. Changes in spirometry over time as a prognostic marker in patients with Duchenne muscular dystrophy. Am J Respir Crit Care Med 2001;164:2191-4. 35. Ugalde V, Breslin EH, Walsh SA, Bonekat HW, Abresch RT, Carter GT. Pursed lips breathing improves ventilation in myotonic muscular dystrophy. Arch Phys Med Rehabil 2000;81: 472-8. *36. Biggar WD, Gingras M, Fehlings DL, Harris VA, Steele CA. Deflazacort treatment of Duchenne muscular dystrophy. J Pediatr 2001;138:45-50. *37. Carter GT, McDonald CM. Preserving function in Duchenne dystrophy with long-term pulse prednisone therapy. Am J Phys Med Rehabil 2000;79:455-8. 38. Packer RJ, Brown MJ, Berman PH. The diagnostic value of electromyography in infantile hypotonia. Am J Dis Child 1982; 136:1057-9. 39. Sacco G, Buchthal F, Rosenfalck P. Motor unit potentials at different ages. Arch Neurol 1962;6:366-73. 40. Gutrecht JA, Dyck PJ. Quantitative teased-fiber and histologic studies of human sural nerve during postnatal development. J Comp Neurol 1970;138:117-29. 41. David WS, Jones HR Jr. Electromyographic evaluation of the floppy infant. Muscle Nerve 1990;13:857. *42. David WS, Johns HR Jr. Electromyography and biopsy correlation with suggested protocol for evaluation of the floppy infant. Muscle Nerve 1994;17:424-30. *43. Renault F, Chartier JP, Harpey JP. [Contribution of the electromyogram in the diagnosis of infantile spinal muscular atrophy in the neonatal period] [French]. Arch Pediatr 1996;3:319-23. *44. Stempien LM. Special considerations in pediatric electromyography. Phys Med Rehabil Clin North Am 1998;9:897-906. 45. Rowinska-Marcinska K, Ryniewicz B, Hausmanowa-Petrusewicz I, Karwanska A. Diagnostic value of satellite potentials in clinical EMG. Electromyogr Clin Neurophysiol 1997;37:483-9. 46. Benstead TJ, Kuntz NL, Miller RG, Daube JR. The electrophysiologic profile of Dejerine-Sottas disease (HMSN III). Muscle Nerve 1990;13:586-92. 47. Strommen JA, Johns JS, Kim CT, et al. Neuromuscular rehabilitation and electrodiagnosis. 3. Diseases of muscles and neuromuscular junction. Arch Phys Med Rehabil 2005;86(3 Suppl 1):S18-27.