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Evaluation, Special Studies
Neuromuscular disorders may cause dramatic disability in the neonatal period. The dominant features of these disorders are muscle weakness and hypotonia. In this context, I consider neuromuscular disorders those that predominantly involve the motor system, from its origins in the cerebral cortex to its termination in the muscle.
This and the next three chapters are concerned with neuromuscular disorders. In this chapter, the motor system is described in terms of its anatomical and physiological organization; special additional emphasis is placed on the development and the biochemical features of muscle. Also, the evaluation of disorders of the motor system in the newborn and the diagnostic studies used in their diagnostic investigation are reviewed in detail.
MOTOR SYSTEM
The control of movement and tone in the human nervous system is highly complex, and major lacunae in knowledge exist in our understanding of this control in the neonatal period. Nevertheless, it is reasonable to expect that the anatomical systems critical for control of movement and tone in the mature nervous system are operative, although undoubtedly to varying extents, in the immature nervous system. In the following discussion, the major components of the central and peripheral nervous systems that are important for the control of movement and tone are briefly reviewed. The discussion is organized in the framework used in the next three chapters for the categorization of diseases that disturb muscle power and tone in the human infant.
Levels Above the Lower Motor Neuron
Control of muscle power and tone begins in the central nervous system at levels above the lower motor neuron ( Box 34.1 ). This control is mediated in largest part by the major motor efferent system, the corticospinal and corticobulbar tracts, often termed the pyramidal system because a major portion of these tracts originates in the pyramidal cells of the motor cortex of the cerebrum. Also important in control, primarily through effects on cerebral cortical motor centers, are the basal ganglia and cerebellum. Certain other descending tracts that have an effect on the lower motor neuron involved in muscle power and tone are the rubrospinal, reticulospinal, and vestibulospinal tracts, sometimes collectively referred to as the bulbospinal tracts .
BOX 34.1
Major Components of the Motor System
Levels Above the Lower Motor Neuron
Corticospinal-corticobulbar tracts
Basal ganglia
Cerebellum
Other components (“bulbospinal”)
Rubrospinal tracts
Reticulospinal tracts
Vestibulospinal tracts
Lower Motor Neuron
Cranial nerve motor nuclei
Anterior horn cells
Peripheral Nerve
Neuromuscular Junction
Presynaptic
Postsynaptic
Muscle
.
Corticospinal and Corticobulbar Tracts
The corticospinal tract is the major efferent system concerned with movement of axial and appendicular musculature; the corticobulbar tract is concerned with movement of muscles innervated by the cranial nerves. The origin of this system in the mature subhuman primate is principally from pyramidal cells, with the following distributions: motor cortex, 31%; premotor cortex, 29%; and parietal lobe, 40%. The topographical representation of the homunculus on the contralateral cerebral cortex (see Fig. 22.13 ) provides an estimate of the somatotopic origin of these fibers. This system descends through the posterior limb of the internal capsule, the cerebral peduncles, and the pontine tegmentum; decussates in the ventral medulla; and then descends in the lateral column of the spinal cord. A small portion of the system does not decussate and descends uncrossed in the anterior column of the spinal cord. The corticospinal tract subserves refined volitional movements, although the precise contribution to movement in the human newborn is not known entirely.
Basal Ganglia
The system of basal ganglia, sometimes categorized by the less precise term extrapyramidal system , principally consists of five major nuclear masses: caudate, putamen, globus pallidus, subthalamic nucleus, and substantia nigra. These nuclei do not project to the lower motor neuron directly but rather influence muscle power and tone primarily by effects on the corticospinal system. The major afferent centers are the caudate and putamen (the corpus striatum), and the major efferent center is the globus pallidus. Output from the globus pallidus is relayed to the cortical motor neurons principally by way of the thalamus.
Cerebellum
The cerebellum is a complex system of neurons concerned with coordination of somatic motor activity, regulation of muscle tone, and mechanisms that influence and maintain posture and equilibrium. Afferent connections are derived from muscle and tendon stretch receptors and the visual, auditory, vestibular, and somesthetic sensory systems and are conveyed principally through the inferior and middle cerebellar peduncles in the brainstem. Efferent connections are conveyed principally through the superior cerebellar peduncle to the red nucleus (and then to the rubrospinal tract), the vestibular nuclei (and then to the vestibulospinal tract), and the thalamus (and then to cerebral cortical motor neurons). Thus the control of movement and tone by the cerebellum ultimately is by way of other motor systems. The hypotonia observed in cerebellar disease may be mediated primarily by decreased muscle fusimotor activity.
Other Components
The other major components of the motor system include the rubrospinal, reticulospinal, and vestibulospinal tracts, sometimes collectively known as the bulbospinal tracts. The nerve fibers of these tracts, unlike most other fibers of the motor system, are myelinated in the third trimester and may play a particularly important role in control of movement and tone in the premature and full-term newborn .
Rubrospinal Tract
The rubrospinal tract originates in the red nucleus in the midbrain, decussates, and then descends in the lateral aspect of the spinal cord. Major afferents are from the cerebellar and cerebral cortices, and the rubrospinal tract projects to nuclei in the brainstem and cerebellum before reaching the spinal cord. The most important function of the rubrospinal tract is the control of muscle tone in flexor muscle groups. It is tempting to speculate that this system is particularly important in the term newborn because of the impressive flexor tone in the limbs (see Chapter 12 ).
Reticulospinal Tracts
Reticulospinal tracts emanate from neurons of the reticular formation in the pontine and medullary tegmentum and descend in the anterior aspect of the spinal cord. Afferents are derived from all sensory systems and from the cerebral cortex. This system has major functional effects on muscle activity and tone, principally through action on the gamma motor neurons in the anterior horn of the spinal cord, which innervate the contractile portions of the muscle spindle. Indeed, the reticulospinal system presumably mediates the impressive changes in tone observed in infants according to the level of alertness.
Vestibulospinal Tract
The vestibulospinal tract arises from the lateral vestibular nucleus and descends in the anterolateral aspect of the spinal cord. Afferents are derived primarily from the labyrinth (and vestibular portion of the eighth nerve) and the cerebellum. An increase in extensor muscle tone is observed with stimulation of the lateral vestibular nucleus. This system may play a role in the newborn in the mediation of reflex activity associated with vestibular input and extensor muscle activity (e.g., tonic neck and Moro reflexes).
Lower Motor Neuron
The suprasegmental influences just described play on the final common pathway of the motor system, the motor unit. The term motor unit refers to the lower motor neuron (i.e., anterior horn cell or brainstem neuron of the cranial nerve nucleus ), the peripheral nerve (or cranial nerve), the neuromuscular junction, and the innervated muscle.
In the spinal cord, anterior horn cells are arranged such that neurons subserving function of extensor muscles are located ventrally, flexor muscles dorsally, proximal muscles laterally, and distal muscles medially. The two major types of efferent neurons are the predominant large cells that innervate striated muscle and the less abundant small cells that innervate the fibers of the muscle spindle, the stretch receptors. The latter are important in determining the activity of stretch (“tendon”) reflexes and receive input from the aforementioned suprasegmental tracts.
Peripheral Nerve
The large anterior horn cells, concerned with innervation of skeletal muscle, exit through the anterior roots to the peripheral nerve . The nerve fibers conduct the nerve impulse with a velocity directly proportional to their diameter and the size of their myelin sheath. (In addition to transmission of the nerve impulse, these fibers transport a variety of compounds, including enzymes, neurotransmitters, organelles, and nutrient materials, to the distal aspect of the fiber.) The terminal aspect of the nerve fiber ramifies into a variable number of smaller fibers that form motor endplates at the neuromuscular junction. The axon of one motor nerve supplies a variable number of skeletal muscle fibers. In the larger muscles involved in postural control, a single anterior horn cell may provide motor endplates to more than 100 muscle fibers. In smaller muscles (e.g., of the thumb) concerned with highly skilled movement, a single anterior horn cell provides endplates for only a few fibers.
Neuromuscular Junction
The neuromuscular junction contains the terminal nerve branch with its specialized presynaptic ending , which lies in a specialized trough of the postsynaptic muscle plasma membrane (sarcolemma). A synaptic cleft separates the two membranes. When the nerve impulse arrives at the presynaptic site, calcium enters the presynaptic axoplasm and causes the release of vesicles of acetylcholine. The neurotransmitter then diffuses across the synaptic cleft, binds with a specific postsynaptic receptor on the sarcolemma, and alters the permeability of the muscle membrane. Depolarization and a muscle action potential result if enough receptors are activated. This electrical signal is transmitted along the muscle membrane and then internally by a system of invaginations of the sarcolemma to provoke the events leading to muscle contraction. The coupling of excitation and contraction is discussed in more detail subsequently.
Muscle
Development
The chronology and major features of the development of skeletal muscle in the human are summarized in Table 34.1 . These features provide information of value in interpreting the pathological significance of specific findings of the muscle biopsy in the newborn and in establishing anatomical correlates for certain developmental changes in muscle function (see subsequent discussion).
TABLE 34.1
Human Muscle Development
Data from Sarnat HB. Ontogenesis of striated muscle. In: Polin RA, Fox WW, Abman SH, eds. Fetal and Neonatal Physiology . 4th ed. Philadelphia: Elsevier, 2001:1924–1947; and Schloon H, Schlottmann J, Lenard HG, Goebel HH. The development of skeletal muscles in premature infants. Eur J Pediatr 1979;131:49–60.
| DEVELOPMENTAL STAGE | TIME (WEEK OF GESTATION) | MAJOR DEVELOPMENTAL EVENTS |
|---|---|---|
| Premyoblastic | 0–5 | Differentiation of mesenchymal cells to myoblasts |
| Myoblastic | 5–8 | Proliferation of myoblasts |
| Myotubular | 8–15 | Formation of syncytium with central nuclei, myofibrils, sarcotubular system, and early endplates |
| Myocyte | 15–20 | Movement of nuclei to periphery |
| Continued synthesis of myofibrils | ||
| Early histochemical differentiation | 20–24 | Differentiation of fiber types I and II; type II fibers predominate |
| Intermediate histochemical differentiation | 24–34 | Increase in size of type II fibers |
| Late histochemical differentiation | 34–38 | Development of equal numbers of fiber types I and II due to marked increase in small type I fibers |
| Mature myocyte | >38 | Increase in size of all muscle fibers |
Premyoblastic Stage
The premyoblastic stage, occurring in the first 5 weeks of gestation, is characterized principally by the differentiation of primitive mesenchymal cells to myoblasts.
Myoblastic Stage
The myoblastic stage, which follows in the next 3 to 8 weeks, is dominated by active proliferation and migration of myoblasts along programmed pathways in synchrony with neural crest migration. Synthesis of the contractile proteins begins.
Myotubular Stage
During the myotubular stage, from approximately 8 to 15 weeks of gestation, myoblasts fuse to form the syncytium characteristic of human skeletal muscle. Nuclei are located centrally, unlike the peripheral location of mature muscle. Myofilaments of the contractile proteins actin and myosin develop the longitudinal organization necessary for formation of myofibrils. The sarcotubular system, the invaginations of the sarcolemma so important in excitation-contraction coupling, is formed. Axonal terminals contact muscle at 9 to 11 weeks, and motor endplates begin to appear at 14 weeks of gestation. The genes myogenin and myomaker are the primary mediators of myoblast fusion; myomaker is known as a late membrane activator of that process.
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