General Features of Hypotonia

Assessing tone in an infant involves both observation of the patient at rest and application of certain examination maneuvers designed to evaluate both axial and appendicular musculature. Beginning with observation, a normal infant lying supine on an examination table will demonstrate flexion of the hips and knees so that the lower extremities are clear of the examination table, flexion of the upper extremities at the elbows, and internal rotation at the shoulders (Fig. 27.1). A hypotonic infant lies with the lower extremities in external rotation, the lateral aspects of the thighs and knees touching the examination table, and the upper extremities either extended down by the sides of the trunk or abducted with slight flexion at the elbows, also lying against the examination table. Evaluation of the traction response is done with the infant in supine position; the hands are grasped and the infant pulled toward a sitting position. A normal response includes flexion at the elbows, knees, and ankles, and movement of the head in line with the trunk after no more than a brief head lag. The head should then remain erect in the midline for at least a few seconds. An infant with axial hypotonia demonstrates excessive head lag with this maneuver (Fig. 27.2), and once upright, the head may continue to lag or may fall forward relatively quickly. Absence of flexion of the limbs may also be seen and indicates either appendicular hypotonia or weakness. The traction response is normally present after 33 weeks postconceptional age. Vertical suspension is performed by placing hands under the infant’s axillae and lifting the infant without grasping the thorax. A normal infant has enough power in the shoulder muscles to remain suspended without falling through, with the head upright in the midline and the hips and knees flexed (Fig. 27.3, A). In contrast, a hypotonic infant held in this manner slips through the examiner’s hands, often with the head falling forward and the legs extended at the knees (see Fig. 27.3, B). Infants with axial hypotonia related to brain injury may also demonstrate crossing, or scissoring, of the legs in this position, which is an early manifestation of appendicular hypertonia. In horizontal suspension, the infant is held prone with the abdomen and chest against the palm of the examiner’s hand. A normal infant maintains the head above horizontal with the limbs flexed, while a hypotonic infant drapes over the examiner’s hand with the head and limbs hanging limply. Other examination findings in hypotonic infants include various deformities of the cranium, face, limbs, and thorax. Infants with reduced tone may develop occipital flattening, or positional plagiocephaly, as the result of prolonged periods of lying supine and motionless.

Fig. 27.1 Normal infant lying supine with legs flexed and arms adducted.

Fig. 27.2 Hypotonic infant demonstrating abnormal traction response, with excessive head lag and absence of flexion of arms and legs.

Fig. 27.3 A, Vertical suspension in a normal infant: arms adducted, upright position of head and shoulders maintained, flexion of legs. B, Ventral suspension in a hypotonic infant, with elevation of shoulders and arms (slip-through) and extension of legs.

Localization

Once the presence of hypotonia in an infant is established, the next step in determining causation is localization of the abnormality to the brain, spinal cord, motor unit, or to multiple sites. A motor unit is a single spinal motor neuron and all the muscle fibers it innervates and includes the motor neuron with its cell body, axon, and myelin covering; the neuromuscular junction; and muscle. The major “branch point” at this stage of the assessment is whether the lesion is likely to be in the brain, at a more distal site, or at multiple sites.

The key features of disorders of cerebral function, particularly the cerebral cortex, are encephalopathy and seizures. Encephalopathy manifesting as decreased level of consciousness may be difficult to ascertain, given the large proportion of time normal infants spend sleeping. However, full-term or near-term infants with normal brain function spend at least some portion of the day awake with eyes open, particularly with feeding. Encephalopathy also manifests with excessive irritability or poor feeding, although the latter problem is rarely the sole feature of cerebral hemispheric dysfunction and may occur with disorders at more distal sites. Infants with centrally mediated hypotonia of many different etiologies frequently have relatively normal power despite a hypotonic appearance. Power may not be observable under normal circumstances because of a paucity of spontaneous movement, but it may be observable with application of a noxious stimulus such as a blood draw or placement of a peripheral intravenous catheter. Other indicators of central rather than peripheral dysfunction include fisting (trapping of the thumbs in closed hands), normal or brisk tendon reflexes, and normal or exaggerated primitive reflexes. Tendon reflexes should be tested with the infant’s head in the midline and the limbs symmetrically positioned; deviations from this technique often result in spuriously asymmetrical reflexes. Primitive reflexes are involuntary responses to certain stimuli that normally appear in late fetal development and are supplanted within the first few months of life by voluntary movements. Abnormalities of these reflexes include absent or asymmetrical responses, obligatory responses (persistence of the reflex with continued application of the stimulus), or persistence of the reflexes beyond the normal age range. Two of the most sensitive primitive reflexes are the Moro and asymmetrical tonic neck reflexes. The Moro reflex is a startle response present from 28 weeks after conception to 6 months postnatal age (Gingold et al., 1998). Quickly dropping the infant’s head below the level of the body while holding the infant supine with the head supported in one hand and the body supported in the other readily elicits this reflex. The normal response consists of initial abduction and extension of the arms with opening of the hands, followed quickly by adduction and flexion with closure of the hands. The tonic neck reflex is a vestibular response and is present from term until approximately 3 months of age. The response is elicited by rotating the head to one side while the infant is lying supine. The normal response is extension of the ipsilateral limbs while the contralateral limbs remain flexed. Central disorders resulting in hypotonia may also be associated with dysmorphism of the face or limbs, or malformations of other organs. Various defects in O-linked glycosylation of α-dystroglycan, a protein associated with the dystrophin glycoprotein complex that stabilizes the sarcolemma, result in structural defects of the brain, eye, and skeletal muscle.

Disorders of the spinal cord leading to neonatal hypotonia are usually secondary to perinatal injury. Spinal cord injury may occur in the setting of a prolonged, difficult vaginal delivery with breech presentation, resulting in trauma to the spinal cord, or may result from hypoxic-ischemic injury to the cord concurrently with encephalopathy. In the latter case, hypotonia may initially be attributable to the encephalopathy. In cases of hypotonia resulting from spinal cord injury, diminished responsiveness to painful stimuli, sphincter dysfunction with continuous leakage of urine and abdominal distension, and priapism may provide clues to localization of the lesion.

The hallmark of disorders of the motor unit is weakness. Tendon reflexes are absent or reduced. Tendon reflexes reduced out of proportion to weakness usually indicate a neuropathy, often a demyelinating neuropathy, whereas tendon reflexes reduced in proportion to weakness are more likely to result from myopathy or axonal neuropathy. The motor unit is the final common pathway for all reflexes, and for this reason, primitive reflexes are depressed or absent in motor unit disorders. This phenomenon may hinder detection of central nervous system (CNS) abnormalities when lesions at both levels coexist. Other abnormalities related to motor unit disorders in infants include underdevelopment of the jaw (micrognathia), a high arched palate, and chest wall deformities, in particular pectus excavatum. Muscle atrophy may also occur but also occurs in cerebral disorders. Sensory function is not assessable in detail in a neonate or young infant, particularly in the presence of encephalopathy, although reduced responsiveness to pinprick may provide clues to the presence of a polyneuropathy or spinal cord lesion in the setting of normal mental status. Some motor unit disorders may result in perinatal distress due to weakness and may result in a superimposed encephalopathy that confounds the localization of hypotonia.

Hypotonic infants may have reduced movement during fetal development, leading to fibrosis of muscles or of structures associated with joints, as well as foreshortening of ligaments. This results in restricted joint range of motion, or contractures. The term arthrogryposis refers to joint contractures that develop prenatally. The most common form of arthrogryposis is unilateral or bilateral clubfoot. The most severe end of this clinical spectrum is arthrogryposis multiplex congenita, or multiple joint contractures. The causes of this condition may be abnormalities of the intrauterine environment, motor unit disorders, or disorders of the CNS. Hypotonia in utero may also result in congenital hip dysplasia.

Neuroimaging

Neuroimaging studies, in particular magnetic resonance imaging (MRI), are most useful when suspecting structural abnormalities of the CNS. T1-weighted images most readily detect congenital malformations of the brain and spinal cord, while T2-weighted images and various T2-based sequences reveal abnormalities of white matter and show evidence of ischemic injury. Specialized techniques such as MR spectroscopy may show evidence of mitochondrial disease (Matthews et al., 1993) or disorders of cerebral creatine metabolism (Frahm et al., 1994). When performing neuroimaging studies that require sedation on hypotonic infants, give particular consideration to airway management and other safety issues.

Electroencephalography

Electroencephalography may be informative when seizures are suspected either as a cause of unexplained encephalopathy or a result of a more global disturbance of brain function. EEG may also reveal evidence of underlying structural abnormalities and thus increase the pretest probability of a diagnostic finding on neuroimaging.

Creatine Kinase

Creatine Kinase catalyzes the conversion of creatine to phosphocreatine, which serves as a reservoir for the buffering and regeneration of adenosine triphosphate (ATP). It expresses in many human tissues, in particular smooth muscle, cardiac muscle, and skeletal muscle. The concentration of CK detectable in serum increases in any condition in which tissues expressing high levels of the enzyme undergo breakdown. Serum CK concentration may be elevated in congenital myopathies, congenital muscular dystrophies, or in spinal muscular atrophy, but levels may also be elevated transiently following normal vaginal deliveries or with perinatal distress. Conversely, serum CK is normal in some congenital myopathies and inherited neuropathies.

Metabolic Studies

Removal of low-molecular-weight toxic metabolites across the placenta typically prevents inborn errors of metabolism (e.g., amino acidopathies, organic acidurias, urea cycle defects, fatty acid oxidation defects, mitochondrial disorders) from causing in utero injury. More commonly, these disorders manifest in a previously healthy newborn who develops hypotonia, encephalopathy, or seizures within the first 24 to 72 hours after birth, after oral feeding begins and toxic intermediates begin to accumulate in the blood. Although detection of many disorders is by state-mandated newborn screens, these results may not be available before an affected infant becomes symptomatic. For this reason, newborns who develop hypotonia and encephalopathy after an unremarkable first few days of life should have enteral feedings held until metabolic studies such as blood ammonia level, plasma amino acid, acylcarnitine profile, and urine organic acids have definitively excluded an inborn error of metabolism. Because neonatal sepsis has a similar presentation, undertake investigation for infection with cultures of blood, urine, and cerebrospinal fluid in such cases; empirical antimicrobial therapy should be initiated while diagnostic studies are pending.

Nerve Conduction Studies and Electromyography

Nerve conduction studies and EMG are the studies of choice in a suspected motor unit disorder when other available clinical information does not suggest a specific diagnosis. The two techniques are complementary and always performed together. They allow distinction between primary disorders of muscle and peripheral nerve disorders when the two are indistinguishable on clinical grounds. Repetitive nerve stimulation (RNS) studies evaluate the integrity of the neuromuscular junction, abnormalities of which are not detectable with routine nerve conduction studies or EMG. The most commonly observed abnormality on low-rate (2-3 Hz) RNS studies of patients with various forms of myasthenia is a significant decrement, usually defined as 10% or greater, in the amplitude of the compound motor action potential (CMAP) between the first and fourth or fifth stimuli of a series. Single fiber EMG (SFEMG) is a highly specialized technique that evaluates the delay in depolarization between adjacent muscle fibers within a single motor unit, referred to as jitter. This modality is highly sensitive for neuromuscular junction abnormalities but has a low specificity and requires a cooperative patient. SFEMG with stimulation of the appropriate nerve has been described in pediatric patients (Tidwell and Pitt, 2007), but experience with this technique in infants is limited to a small number of centers. The utility of these neurophysiology studies is dependent on the skill and experience of the clinician performing the tests, as well as the precision of the question posed.