Hypotonia is defined as reduced resistance to passive range of motion in joints generated by an alert, but not overstimulated subject.1,2 Hypotonia is caused by a wide variety of disorders involving the central and peripheral nervous system. It is therefore clinically classified as central and peripheral types. Central hypotonia can result from ischemic and hemorrhagic brain insults, congenital brain malformations, genetic syndromes, and inborn errors of metabolism. Peripheral hypotonia can be caused by abnormalities in the anterior horn cell, peripheral nerves, neuromuscular junction, and muscle.1 The central type is more common than the peripheral type, accounting for 65% to 85% of cases.1–5
It is reasonable to assume an association between hypotonia and motor development. In a survey of 268 physical and occupational therapists, 80% stated that delayed motor development is evident in children with hypotonia.6 There are, however, only a few studies on the relationship between hypotonia and motor development, and most of them used nonstandardized motor development assessments and did not evaluate the contribution of axial versus appendicular hypotonia.7–10
The current study applied an objective developmental measure to investigate the relationship between hypotonia and motor development in a cohort of infants with central hypotonia who were attending a high-risk neonatal neurology clinic. Our objectives were to determine an association between hypotonia and motor development, and the relative contribution of nuchal, truncal, and appendicular hypotonia to motor development.
Study Design and Subjects
We retrospectively studied infants referred to our neonatal neurology clinic between August 2004 and December 2008. The patient population included term and preterm infants with an acquired or congenital neurologic disorder diagnosed during the fetal or neonatal period who were considered as being at risk for neurodevelopmental sequelae. Inclusion criteria were infants with either normal muscle tone or those with central hypotonia defined as hypotonia of the axial and/or appendicular muscles, with normal or brisk deep tendon reflexes and without muscle weakness.11 In addition, only infants who had undergone evaluations by both a pediatric neurologist and a physical therapist on the same day were included. We excluded infants with peripheral (lower motor neuron) hypotonia, weakness (ie, reduced antigravity movements and/or decreased active resistance to force exerted by the examiner), and those with hypertonia. The tone of limbs, trunk, and neck muscles was scored by one pediatric neurologist (Haim Bassan) and categorized as normal, reduced, or increased (see tone criteria below). One physical therapist (Tali Peylan) administered the psychomotor developmental index (PDI) of the Bayley Scales of Infant Development, 2nd edition.12 Age at testing was adjusted for prematurity for all infants younger than 24 months. This study was approved by the ethics committee of the medical center.
Tone Assessment. During tone assessment, the infant was calm but alert and not overstimulated. The following criteria were used for tone assessment:
- 1a. Nuchal hypotonia: head lag on pull-to-sit maneuver, head bobbing or drop on sitting position, head drop on ventral suspension.
- 1b. Nuchal hypertonia: dorsal extension, above neutral position, of the neck on a lateral recumbent position and on ventral suspension.
- 2a. Truncal hypotonia: slipping on axillary suspension and back curving on sitting position.
- 2b. Truncal hypertonia: firm, strong resistance of shoulders, back extension on lateral position.
- 3a. Appendicular hypotonia: decreased limb resistance while opposing passive movements, increased limb floppiness upon limb shake-up.
- 3b. Appendicular hypertonia: determined when the Ashworth scale13 (range 1-5) was 2 or more.
The tone scores were clinically categorized into 3 domains: truncal, nuchal, and appendicular. All subjects with hypertonia were excluded. Each tone domain received a binary score of 0 (normal) or 1 (hypotonia).
Psychomotor Developmental Index. The PDI of the Bayley Scales of Infant Development, 2nd edition,12 was administered by a physical therapist. The PDI assesses the gross and fine motor skills, with a standardization mean of 100 and a standard deviation of 15 points.
Medical History. The relevant clinical data collected from the infant's chart included demographics, clinical diagnosis, and neuromotor outcome after 2 years of age, defined as a diagnosis of cerebral palsy (CP), according to Hagberg et al.14,15 The parents of 40 infants with incomplete outcome data were contacted by one of the investigators and queried about outcome verification.
Data were analyzed using SPSS for Windows (SPSS Inc, Chicago, Illinois) and SAS (SAS Inc., Cary, North Carolina). Significance was set at P < .05. The proportional relationship between the 3 hypotonia domains was automatically drawn by eulerAPE software (http://www.eulerdiagrams.org). For the purpose of statistical analysis, the cohort was divided into 4 PDI categories: 1 = normal (>100), 2 = low normal (85-100), 3 = mild impairment (70-84), and 4 = significant impairment (<70). Each of the 3 tone domains (truncal, nuchal, and appendicular) was compared across the 4 PDI categories using the chi-square test.
We then generated a total hypotonia score on the basis of each the 3 tone domains (nuchal, truncal, and appendicular): the presence of hypotonia yielded a score of 1 and normal tone yielded a score of 0. Thus, an infant with normal tone in all 3 domains received a total hypotonia score of 0, whereas an infant with hypotonia of all 3 domains received a total hypotonia score of 3. Group comparisons of mean ± standard deviation PDIs across the total hypotonia scores were analyzed using analysis of variance. The effects of each of the 3 hypotonia domains on the PDI were finally tested by a linear analysis adjusted for gestational age and birth weight percentile, and age at examination. A multivariate regression model was not applied because of collinearity between the hypotonia tone domains.
Spearman's correlation analysis was applied to study the relationship between PDI scores and hypotonia domains and a diagnosis of CP.
We evaluated 195 potential subjects with the results of same-day tone and PDI examinations extracted from our neonatal neurology high-risk clinic database. Twenty-seven infants with hypertonia were excluded. Also excluded were 4 infants with peripheral hypotonia: Duchenne muscular dystrophy (n = 1), congenital myotonic dystrophy (n = 1), and myelomeningocele (n = 2). A total of 164 high-risk infants comprised the final study cohort. Their demographics and clinical diagnoses are presented in Table 1. Their mean age at study was 9.6 ± 4 months. Thirty-six of the 164 high-risk infants had a normal tone in all 3 tone domains. Central hypotonia was diagnosed in 128 infants: 26 (20.3%) had hypotonia in 1 tone domain and 102 (79.7%) had multiple combinations of 3 hypotonia tone domains (Figure 1). Truncal hypotonia was the most commonly diagnosed domain (115 infants). Appendicular and nuchal hypotonia were diagnosed in 93 and 70 infants, respectively.
Central hypotonia as well as its 3 domains (nuchal, truncal, and appendicular) was significantly associated to the 4 ordinal PDI score categories (Table 2). Group comparisons of mean PDI scores ± standard deviation across each of the total hypotonia scores revealed a significant relationship between them: score 0 (PDI = 95.3 ± 17.1), score 1 (PDI = 83.7 ± 15.6), score 2 (PDI = 82.2 ± 18.7), and score 3 (PDI = 71.7 ± 16.5), P < .001 (Figure 2). Each of the 3 tone domains was significantly associated with PDI scores on the adjusted linear regression analysis (P < .001). Nuchal hypotonia had the strongest β-coefficient (β = −0.6), P < .001, whereas the contribution of appendicular and truncal hypotonia was weaker (β = −0.45 and −0.4 respectively), P < .001 (Table 3).
Nine of the 164 infants (5.5%) were diagnosed as having CP after 2 years of age. CP types were quadriparetic (n = 2), dyskinetic (n = 1), ataxic-hypotonic (n = 1), hemiparetic (n = 2), and diplegic (n = 3). The PDI scores correlated significantly with a later diagnosis of CP (r = −0.24, P = .002). No correlation was found between any of the 3 tone categories and a later diagnosis of CP.
Our data show that central hypotonia is significantly associated with lowered motor developmental scores. Of the 3 tone domains, nuchal tone had the highest association with motor development. Contrary to the expected increase in muscle tone in an upper motor neuron lesion, hypotonia may be the dominant clinical sign in early infancy.16 This type of hypotonia is termed central, denoting its origin from central nervous system disorders.4 Later in childhood, some of these infants may remain hypotonic or develop the characteristic hypertonia associated with an upper motor neuron lesion, whereas others may demonstrate “transient” hypotonia and have normal tone later in childhood.
In the current work, we studied a group of high-risk infants with upper motor neuron processes, including ischemic, hemorrhagic, inflammatory, developmental, and genetic disorders. One-quarter of our subjects were referred solely due to prematurity, without an apparent neurological complication. Although a clinical diagnosis of central hypotonia is common in everyday practice of physical therapists and pediatric neurologists, there are no validated hypotonia scoring systems and its final diagnosis is primarily based on subjective assessment.6 We therefore did not aim to quantify hypotonia, but rather used a consistent clinical hypotonia diagnosis protocol that was administered by one investigator to all subjects. Our results showed that central hypotonia involved the truncal muscles to a greater extent than appendicular muscles, a finding previously described by others.16 Truncal and appendicular hypotonia tended to coexist; however, hypotonia of the neck was most commonly accompanied by truncal and not by appendicular hypotonia. This combination of truncal and neck hypotonia comprises the characteristic features of axial muscle hypotonia.
The literature on the correlation between hypotonia and motor development is sparse.3 Our finding of a significant correlation between central hypotonia and delayed motor development corroborates with the study of Paine et al5 of 133 infants with central and peripheral hypotonia who presented with motor delays. Others have reported an association between hypotonia and gross motor delay.7–9 The majority of infants in those reports had a later catch-up in motor development, suggesting a benign congenital hypotonia variant.
Contrary to our findings, Pilon et al10 found no association between hypotonia and motor development in a group of apparently healthy 141 infants. Our results are not entirely comparable with theirs; however, because most of their population included normally developing term infants, while our population consisted of preterm and term high-risk infants with central hypotonia, most of whom carry a neurologic diagnosis. In addition, tone assessment in our study included nuchal, truncal, and appendicular tone, whereas their study was primarily based on appendicular tone assessment.
The relationship between hypotonia and motor development may be explained by the biomechanical effect that hypotonia could have on the quality of postural responses and on motor performance in general. Our findings do not, however, necessarily imply causality. Disorders of the central nervous system may lead in parallel to both hypotonia and motor delays. For the clinician, recognizing the association between central hypotonia and motor development may point to a therapeutic plan with focused attention on physical therapy and motor development.
The specific delineation of truncal, nuchal, and appendicular tone allowed us to observe that nuchal hypotonia in combination with either truncal and\or appendicular hypotonia, had the strongest contribution to motor developmental scores. Nuchal tone and its resultant head control is, indeed, pivotal for various developmental functions, including those involving vision, hearing, oromotor skills, neuromotor functions of the trunk and arms, and social skills.17 The common association between nuchal and truncal hypotonia may imply that their combination is of greater clinical importance. Taken together, these data could form the basis for future studies designed to enhance head and trunk control as a key element in the paradigm of neuromotor developmental intervention. We recognize that our research was not designed to study the relationship between tone and follow-up outcome. Only 5.5% of our infants developed CP. Therefore, our finding of no correlation between any of the 3 tone categories and a later diagnosis of CP should be taken as preliminary and await confirmation by larger follow-up studies.
Our study group has heterogenous pathologies and consists of multiple etiologies of central hypotonia. However, this heterogeneity can also be considered a strength in that it represents the typical high-risk neonatal neurology clinic with a relatively large number of infants with central hypotonia. As a retrospective analysis, our study has several potential limitations. Although tone and PDI were each assessed by one experienced investigator, we did not use a validated hypotonia protocol, information regarding intrarater reliability was not available, and the study investigators were not blinded to the infant's clinical information. We, additionally, do not have the detailed outcome information for the entire cohort. Notably, joint hyperlaxity was not assessed in this study. We assume that joint hyperlaxity may sometimes have contributed to our perception of hypotonia, although the existing literature on the association between joint hyperlaxity and motor development is contradictory.18,19
The findings of the current study on high-risk infants demonstrate a significant association between central hypotonia and motor development measured at the same point in time. Hypotonia was not, however, correlated with a later diagnosis of CP. We also show that nuchal hypotonia contributed to motor developmental scores more strongly than truncal and appendicular hypotonia. These data can be useful for future intervention trials for hypotonic high-risk infants with a therapeutic plan that targets nuchal hypotonia to enhance the infant's motor abilities and neurodevelopmental outcome.
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Keywords:Copyright © 2016 Academy of Pediatric Physical Therapy of the American Physical Therapy Association
appendicular; axial; motor development; neck; tone; truncal