Accepted Manuscript Improvement of upper extremity motor control and function after home-based constraint-induced therapy in children with unilateral cerebral palsy: Immediate and long-term effects Hsieh-ching Chen, PhD Chia-ling Chen, MD, PhD Lin-ju Kang, PhD Ching-yi Wu, ScD, OTR Fei-chun Chen, MS Wei-hsien Hong, PhD PII:
S0003-9993(14)00266-4
DOI:
10.1016/j.apmr.2014.03.025
Reference:
YAPMR 55796
To appear in:
ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
Received Date: 18 August 2013 Revised Date:
17 March 2014
Accepted Date: 27 March 2014
Please cite this article as: Chen H-c, Chen C-l, Kang L-j, Wu C-y, Chen F-c, Hong W-h, Improvement of upper extremity motor control and function after home-based constraint-induced therapy in children with unilateral cerebral palsy: Immediate and long-term effects, ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION (2014), doi: 10.1016/j.apmr.2014.03.025. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Running head: Motor Control and Constraint-Induced Therapy in CP
Improvement of upper extremity motor control and function after home-based
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constraint-induced therapy in children with unilateral cerebral palsy: Immediate and
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long-term effects
Hsieh-ching Chen,a* PhD; Chia-ling Chen,b,c* MD, PhD; Lin-ju Kang,c PhD; Ching-yi Wu,d
a
Hsieh-ching Chen and Chia-ling Chen contributed equally to this manuscript.
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ScD, OTR; Fei-chun Chen,c,e MS, Wei-hsien Hong,f PhD
Department of Industrial Engineering & Management, National Taipei University of
Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital,
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Technology, 1 Chung-hsiao E. Rd., Sec. 3, Taipei 106, Taiwan
Linkou, 5 Fu-Hsing St., Kwei-Shan, Tao-Yuan 333, Taiwan c
Graduate Institute of Early Intervention, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Rd., Kwei-Shan, Tao-Yuan 333, Taiwan
d
Graduate Institute of Behavioral Sciences and Dept. of Occupational Therapy, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Rd., Kwei-Shan, Tao-Yuan 333, Taiwan
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Buddhist Tzu Chi General Hospital, 289 Jianguo Rd., Xindian, New Taipei City 231, Taiwan
f
Department of Sports Medicine, China Medical University, 91 Hsueh-Shih Rd., Taichung
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40402, Taiwan
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To whom correspondence, proofs and reprints requests should be made:
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Chia-ling Chen, MD, PhD Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Linkou
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5 Fu-hsing St., Kwei-shan, Tao-yuan 333, Taiwan E-mail: [email protected]
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Word counts: main text- 4,862 words; Abstract- 274 words
Source of support: the National Science Council [NSC 102-2410-H-182-018, NSC 101-2314-B-182-004-MY3] and Chang Gung Medical Foundation [CMRPG 391671-3] in Taiwan.
Financial disclosure: We certify that no party having a direct interest in the results of the
ACCEPTED MANUSCRIPT research supporting this article has or will confer a benefit on us or on any organization with which we are associated AND, we certify that all financial and material support for this
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research and work are clearly identified in the title page of the manuscript.
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Clinical trial registration number: ClinicalTrials.gov ID No. NCT01076257
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Acknowledgments: The authors would like to thank the National Science Council [NSC 102-2410-H-182-018, NSC 101-2314-B-182-004-MY3] and Chang Gung Medical Foundation [CMRPG 391671-3] for financially support. Ted Knoy is appreciated for his
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editorial assistance.
ACCEPTED MANUSCRIPT Improvement of upper extremity motor control and function after home-based
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constraint-induced therapy in children with unilateral cerebral palsy: Immediate and
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long-term effects
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ACCEPTED MANUSCRIPT Abstract
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Objective: To investigate the long-term effects of home-based constraint-induced therapy
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(hCIT) on motor control underlying functional change in children with unilateral cerebral
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palsy (CP).
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Design: A randomized controlled trial.
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Setting: Home-based.
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Participants: Forty-five children with unilateral CP (aged 6–12 years) were randomly
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assigned to receive hCIT (n = 23) or traditional rehabilitation (TR) (n = 22).
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Interventions: Both groups received a 4-week therapist-based intervention at home. The
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hCIT involved intensive functional training of the more affected upper extremity while the
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less affected one was restrained. The TR involved functional unimanual and bimanual
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training.
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Main Outcome Measures: All children underwent kinematic and clinical assessments at
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baseline, 4 weeks (post-treatment), and 3 and 6 months (follow-up). The reach-to-grasp
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kinematics were reaction time (RT), normalized movement time (nMT), normalized
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movement unit (nMU), peak velocity (PV), maximum grip aperture (MGA), and percentage
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of movement where MGA occurs (PMGA). The clinical measures were the Peabody
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Developmental Motor Scale 2 (PDMS-2), Bruininks-Oseretsky Test of Motor Proficiency
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(BOTMP), and Functional Independence Measure for children (WeeFIM).
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ACCEPTED MANUSCRIPT Results: The hCIT group showed a shorter RT (p < 0.050) and nMT (p < 0.010), smaller
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MGA (p = 0.006), and fewer nMU (p = 0.014) in the reach-to-grasp movements at
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post-treatment and follow-up than the TR group. The hCIT group improved more on the
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PDMS-2 (p < 0.001) and the WeeFIM (p < 0.010) in all post-treatment tests and on the
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BOTMP (p < 0.010) at follow-up than the TR group.
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Conclusions: The hCIT induced better spatial and temporal efficiency (smoother movement,
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more efficient grasping, and better movement preplanning and execution) for functional
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improvement up to 6 months after treatment than the TR.
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Key Words: Cerebral palsy; Constraint-induced therapy; Kinematic analysis; Functional
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outcome; Randomized controlled trial
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CP, cerebral palsy
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CIT, constraint-induced therapy
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hCIT, home-based constraint-induced therapy
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PDMS-2, Peabody Developmental Motor Scale–2nd edition
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PDMS-G, Peabody Developmental Motor Scales-grasping subscale
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PDMS-VMI, Peabody Developmental Motor Scales-visual motor integration subscale
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BOTMP, Bruininks-Oseretsky Test of Motor Proficiency
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WeeFIM, Functional Independence Measure for Children
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WeeFIM-SC, Functional Independence Measure for Children -self-care subscale
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RT, reaction time
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nMT, normalized movement time
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nMU, normalized movement unit
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PV, peak velocity
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MGA, maximum grip aperture
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PMGA, percentage of movement where MGA occurs
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Cerebral palsy (CP) is a major childhood disability.1 The motor disorders of CP are often associated
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sensation,
perception,
cognition,
communication,
behavior,
and
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musculoskeletal problems.2 Children with unilateral or hemiparetic CP often present with
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unilateral spasticity, weakness, early asymmetry in movements and/or functional abilities (i.e.,
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asymmetrical crawl or early hand preference), and a high rate of partial seizures.1 The upper
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extremities are often more involved than the lower extremities in children with unilateral CP.2
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Children with unilateral CP typically learn strategies and techniques to perform daily tasks
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with one hand.3 Children with unilateral CP typically do not use their more affected upper
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extremity. They frequently use their less affected upper extremity to increase the efficiency of
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performing tasks, which is called developmental disregard.3-5 These problems further limit the
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daily activities and participation of children with unilateral CP.
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Constraint-induced therapy (CIT) is an intervention approach for treating developmental
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disregard in patients with unilateral motor involvement.6-7 CIT involves intensive functional
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training and shaping for the more affected upper extremity, a constraint for the less affected
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upper extremity, and a behavioral technique termed 'transfer package'.6, 8 The component of
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the ‘transfer package’ in CIT could facilitate turning the therapeutic gains achieved in the
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clinic into real-world activities and retention of the treatment effects 6 months later.8 The aim
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of CIT is to reverse the behavioral suppression of the movement of the more affected upper
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extremity.3 Several systematic review studies3, 7, 9 and randomized controlled trials (RCTs)4, 6,
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10-13
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living in children with CP.
have demonstrated that CIT improves the functional performance and activities of daily
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Home-based CIT (hCIT) places the practice in a natural context and is the preferred
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method for the treatment of children with CP over clinic-based CIT.14 A home environment
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can enhance motivation, engagement, and repetition in everyday activities for children.15-17
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Home-based therapy can facilitate the transfer of the training effects of CIT to daily life 18 and
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may also enhance greater ‘transfer package’ effects than clinic-based CIT. Furthermore, the
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hCIT protocol, with its relatively moderate intensity and shortened constraint time, might
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balance the effectiveness and compliance of the children and caregivers.13, 19-20 Therefore,
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hCIT may be an effective alternative to conventional CIT.13, 19-20
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Therapies for upper extremity dysfunction in children with CP typically target functional
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outcomes and underlying motor control impairments. Kinematic analysis can reveal the motor
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control strategies underlying the performance of motor tasks. Reach and reach-to-grasp are
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fundamental motor tasks that a child needs to interact with his surrounding environment in
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daily living. The kinematic parameters of a reach task, such as reaction time (RT), normalized
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movement time (nMT), and normalized movement units (nMUs), can provide information on
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reach-to-grasp task can provide additional information on grip formation, such as the
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maximum grip aperture (MGA) and the percentage of movement time during which
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maximum grip aperture (PMGA) occurs. High efficiency of a reach-to-grasp task is
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characterized by a short RT and nMT (movement preplanning and execution), few nMUs
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(increased movement smoothness), a small MGA (minimal hand opening while grasping),
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and a high PMGA.23 Research has demonstrated that CIT produces a greater improvement in
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motor control on reaching or reach-to-grasp tasks and functional performance in stroke
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patients than traditional rehabilitation (TR) therapy.21-23 In this study, the RT, nMT, nMU,
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MGA, and PMGA were selected for kinematic analysis because these parameters indicate the
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ability to complete the functional tasks smoothly and efficiently.20-23
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Previously we compared hCIT with TR and examined the effects of hCIT on the motor
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performance of children with CP over different time frames. Subsets of data from this study
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have been published in our previous two manuscripts.19-20 In the first manuscript,19 we used
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only those children from this data set who were 6-8 years of age and compared the
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effectiveness of hCIT with TR
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Developmental Motor Scale-2nd edition (PDMS-2)24 and the Pediatric Motor Activity Log
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(PMAL)25 were selected as the main functional outcome measures. We found that hCIT
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at post-treatment and at 3-month follow-up. The Peabody
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at both times. In the second manuscript,20 we used all children from this data set and focused
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on examining the effects of hCIT on reaching kinematics by using a simple reach task at
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post-treatment, but not at follow-ups. The Bruininks-Oseretsky Test of Motor Proficiency
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(BOTMP)26 and PMAL were used as the main functional outcome measures.20 We found that
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hCIT induced greater temporal and spatiotemporal efficiency in the short term, as
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demonstrated by shorter RT and nMT and higher peak velocity (PV) compared with TR.20
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However, there have been no studies investigating the long-term changes in motor control
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strategies after CIT in children with CP using a more complex reach-to-grasp task (e.g., reach
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and grasp a ball or can) rather than a simple reach task (e.g., reach and press a bell or button).
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The long-term effects of either CIT27-29 or hCIT13, 19 on the motor function of children
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with CP have already been established. To the best of our knowledge, the long-term effects of
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hCIT on the motor control strategies of children with CP have not yet been elucidated.
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Therefore, the current study is a follow-up RCT to our two previous studies.19-20 We compared
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both the immediate (post-treatment) and maintained (3-month and 6-month) effects of hCIT
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and TR therapy by combining the kinematic analysis of a reach-to-grasp task and clinical
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evaluations. We will determine whether functional improvement is accompanied by changes
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in motor control in both short- and long-term time frames. For this study, the
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ACCEPTED MANUSCRIPT Bruininks-Oseretsky Test of Motor Proficiency (BOTMP)26 and the PDMS-224 were selected
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as the primary outcome measures. The Functional Independence Measure for Children
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(WeeFIM)30 was used as the secondary outcome measure. The rationale for using
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dose-matched interventions for both groups is based on RCTs of CP13,19-20 and stroke.21-23 We
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hypothesized that hCIT would generate greater functional gains accompanied by better motor
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control strategies (shorter RT and nMT, fewer nMUs, smaller MGA and PMGA, and larger
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PV) of reach-to-grasp than TR in both the immediate phase (at post-treatment) and the
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maintenance phase (at 3- and 6-month follow-ups). The study findings will help clinicians
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elucidate the neuro-motor control strategies underlying functional improvement after hCIT.
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METHODS
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Participants
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Children with CP aged 6–12 years from the Department of Physical Medicine and
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Rehabilitation of a tertiary medical center were recruited for this study. The
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inclusion/exclusion criteria were reported in our previous manuscript.20 Briefly, the inclusion
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criteria included a diagnosis of congenital unilateral spastic CP, considerable nonuse of the
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more affected upper extremity, active extension movement of the wrist and metaphalangeal
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joint ≥ 10°, and no excessive muscle tone of the more affected upper extremity. The exclusion
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not typically associated with CP, active medical conditions, and any major surgery or nerve
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blockage in the previous 6 months prior to the exposure to CIT. Ethical approval was
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provided by the Institutional Review Board for Human Studies of Chang Gung Memorial
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Hospital (No. 97-1823B) and registered under ClinicalTrials.gov ID No. NCT01076257.
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Caregivers of all participants gave written informed consent.
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Design
This was a single-blinded randomized controlled trial (Figure 1) as reported in our two previous manuscripts.19-20 All children who participated in the study were randomly assigned
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to either the hCIT or the TR group. Among the 75 eligible candidates, a total of 45 children
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with spastic unilateral CP (23 in the hCIT group and 22 in the TR group) were included in the
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final analysis. Children were first stratified by age into two strata (6–8 years and 9–12 years).
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The cut-off age was 8 as the fine finger force coordination in children grasping objects
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approximated that of adults by 8 years old.31-32
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The randomization procedure was reported in our previous manuscript.20 Each age strata
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had a set of sealed envelopes to facilitate the randomized allocation of 45 children into either
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the hCIT or TR groups. There were two sets of envelopes in total, and each set contained 30
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sealed envelopes labeled from 1 to 30 with a group allocation (hCIT or TR).
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measures (primary and secondary outcomes) in a laboratory setting before the intervention
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(pretreatment). An occupational therapist blinded to the group assignment was trained to
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administer these outcome measures. All children underwent these assessments again at 4
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weeks immediately after the intervention (post-treatment), at a 3-month follow-up, and at a
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6-month follow-up. The children’s demographic characteristics, the more affected upper
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extremity, the level of bimanual fine motor function (BFMF),33 and the constraint time (in the
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hCIT group only) were recorded.
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Details of the interventions have been described in our previous manuscript.20 Both
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groups received individualized home-based interventions of 3.5–4 hours/day, twice weekly
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for 4 weeks. One certified physical therapist provided treatments to all the children. The hCIT
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approach adopted in this study may reduce the treatment dosage and constraint time needed to
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achieve benefits by enhancing participant compliance.19-20 The hCIT program focused on the
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and repetitive task practice. Children in the hCIT group were required to wear an elastic
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bandage and a restraint mitten on the less affected upper extremity for 3.5–4 hours/day for 4
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weeks, and their parents were asked to document the number of restraint hours. Children in
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the TR group were engaged in functional unilateral or bilateral upper extremity training using
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the principles of an activity-oriented approach, neurodevelopment treatment techniques, and
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motor learning and control. Both groups continued their usual clinic-based rehabilitation
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programs. Between treatment sessions, children in both groups were encouraged to exercise
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or perform daily activities under parental supervision, such as reaching or grasping objects,
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manipulating their own toys, eating, writing, drawing, and tool usage. Children in hCIT group
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were encouraged to exercise or perform daily functional activities with the more affected
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upper limb, while those in TR group performed daily activities with unilateral or bilateral
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upper limbs.
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Outcome Measures
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Primary outcomes
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Subtest 8 of the BOTMP (BOTMP-sub8),26 which includes 8 items, was used to evaluate
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upper extremity speed and dexterity. Subtest 8 assesses the ability of the child to move and
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such as placing pennies, sorting cards, stringing beads, displacing pegs, drawing lines, and
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marking dots.26 The BOTMP-sub8 was selected because this subtest measures upper
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extremity speed and dexterity during a variety of reach-to-pinch and hand manipulating
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movements. The unimanual tasks on the BOTMP were measured with the more affected
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upper extremity.
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The fine motor domain of the PDMS-2 was used to assess upper extremity functional
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ability.24 The grasping subscale (PDMS-G), which includes 26 items, was selected to assess
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grasping, releasing, and manipulating skills. Unimanual tasks were performed with the more
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affected upper extremity. The BOTMP and PDMS-2, in which higher raw scores indicate
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better performance, have well-established psychometric properties for the total scale and for
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each subscale in children with motor disabilities.24, 26 The PDMS-G was selected because it
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measures functional grasping skills that correspond to the reach-to-grasp kinematic task.
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Secondary outcomes
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The WeeFIM30 includes three functional subscales: self-care, mobility, and cognition.
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The level of independence is rated by a 7-level ordinal rating system ranging from 7
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(complete independence) to 1 (total assistance). The self-care subscale (WeeFIM-SC), which
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pertains to upper limb functions, was selected to measure the performance in daily activities.
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The responsiveness of the WeeFIM instrument has been shown to document changes in the
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functional abilities of children with chronic developmental disabilities.30
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Details of the experimental set-ups for the kinematic analyses have been described in our
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previous manuscript.20 During the reach-to-grasp task (Figure 2), the child sat on a chair
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adjacent to a table with his/her trunk secured to the chair by a harness. The child rested the
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affected hand on a pressure-sensitive hand switch located in line with the child’s affected side.
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A ball 8 cm in diameter was positioned along the child’s midsagittal plane. The distance to
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reach the ball was standardized to the child’s arm length. If the maximum distance the child
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could reach was less than his/her arm length, the distance to reach the ball was adjusted to the
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maximum reachable distance. The child was instructed to reach, grasp, and lift the ball at
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his/her own speed. A start signal was used to start the task.
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Reference markers were placed on the distal interphalangeal joints of the thumb and
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index finger, the styloid process of the ulna, the proximal end of the second metacarpal at the
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base of the 2nd finger, and the ball. An eight-camera motion analysis system (Vicon MX 3-D;
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Oxford Metrics Inc., Oxford, UK) was used to capture the movement of these reference
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connected to the hand switch was used to identify movement onset. The reference marker
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attached to the ball was used to determine movement offset. Movement recording began when
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the child’s hand moved off of the switch and terminated when the marker attached to the ball
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moved.23
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Data Reduction and Data Analysis
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The kinematic data from the reach-to-grasp movements were processed by an analytical
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program coded in LabVIEW (National Instruments Corp., Austin, TX, USA). The parameters
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were as follows: RT, nMT, nMUs, PV, MGA, and PMGA.23 The RT is the interval from the
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start signal to movement onset,34 MT is the interval between movement onset and movement
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completion (i.e., lifting the ball),23, 35-36 and MU is used to characterize movement smoothness
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and the control strategy of reaching that is extracted from the ulnar styloid data. One MU
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comprises one acceleration phase and one deceleration phase. Normalization of MT and MU
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was performed to adjust for differences in reaching distance.23 PV is defined as the highest
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instantaneous velocity during the movement. MGA, a measure of the extent of hand opening,
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was defined as the maximum distance between the thumb and index finger. PMGA, in which
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maximum grip aperture occurs, is a measure of the online correction of target grasping during
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online correction of target grasping.37 A small MGA indicates greater spatial efficiency due to
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less hand opening needed for grasping objects.37 A small MGA is often considered to be
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better because the child can grasp the objects with a relatively small aperture.
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Statistical Analysis
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All statistical analyses were conducted using the SPSS 12.0 software (SPSS, Inc.,
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Chicago, IL, USA). To determine the comparability of the demographic and clinical
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characteristics at baseline, an independent two-sample t-test was applied for continuous
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variables, and a chi-square test was applied for categorical variables. Analysis of covariance
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(ANCOVA), while controlling for pretest differences, was used to determine whether the
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hCIT group performed significantly better than the TR group for each outcome variable
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(reach-to-grasp kinematics and scores for the PDMS-2, BOTMP, and WeeFIM). During each
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analysis, the pretest performance was controlled as a covariate, the group was the independent
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variable, and the post-treatment performance was the dependent variable. The significance
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level was set to 0.050. The effect size, η2, was calculated for each outcome variable to reflect
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the magnitude of the between-group differences. A large effect is represented by an η2 of at
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least 0.138, a moderate effect by an η2 of 0.059, and a small effect by an η2 of 0.010.38
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RESULTS Among the 48 children who initially participated in this study, one child in the TR group
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was unable to complete the follow-up due to a tight family schedule and lack of transportation
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to the site of the posttest assessments (Figure 1). One child in each of the hCIT and TR groups
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was excluded from the analysis because their motor ability was insufficient to complete the
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standardized study procedure of the reach-to-grasp kinematic analysis. Consequently, a total
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of 45 children, 23 in the hCIT group and 22 in the TR group, completed the intervention,
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posttest, and follow-up measures.
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Demographic and Baseline Characteristics
The demographic characteristics of these two groups were comparable (Table 1). The
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pretest results indicated that no differences existed between the two groups in the scores for
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functional measures and reach-to-grasp kinematics, except for the nMU and PMGA scores.
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The hCIT group had greater nMUs and lower PMGAs than the TR group (p = 0.007–0.037).
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Primary Outcomes The PDMS-G and BOTMP-sub8 scores at all post-treatment times for both groups were
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improved more than the TR group on the PDMS-G at not only the post-treatment but also
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both follow-ups (3 and 6 months), with large effects (η2 = 0.604–0.658, p < 0.001).
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Furthermore, the hCIT group has also shown greater improvement than the TR group on the
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BOTMP-sub8 at the 3- and 6-month follow-ups, with large effects (η2 = 0.167–0.193, p =
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0.003–0.006), but not at post-treatment.
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For the daily activity assessments, the WeeFIM-SC scores for both groups improved at
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not only the post-treatment but also both follow-ups (Table 2). The ANCOVA results
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indicated that the hCIT group improved more than the TR group on the WeeFIM-SC at
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post-treatment and both follow-ups, with large effects (η2 = 0.195–0.264, p < 0.001 to p =
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0.003).
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Reach-to-grasp Kinematics
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Both groups had improved reach-to-grasp kinematics at both post-treatment and the
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follow-ups (Table 3). Relative to the TR group, the hCIT group improved more in RT (η2 =
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0.133–0.221, p = 0.001–0.015) and nMT (η2 = 0.158–0.601, p < 0.001 to p = 0.008) at both
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the post-treatment and the follow-ups, with large effects. Additionally, the hCIT group
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moderate effect (η2 = 0.136, p = 0.014), but not at post-treatment or the 3-month follow-up.
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Moreover, the hCIT group improved more than the TR group with respect to MGA at
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post-treatment, with a large effect (η2 = 0.169, p = 0.006), but not at the 3- and 6-month
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follow-ups. The PV and PMGA scores did not differ between the two groups.
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This study is the first, to the best of our knowledge, to reveal the long-term effects of
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hCIT on motor control strategies by using reach-to-grasp kinematics in combination with
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functional improvement in children with CP. Other related studies usually focused only on
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functional improvement. Compared with TR, the hCIT group improved more on the
331
functional outcomes, as measured by the PDMS-G, BOTMP-sub8, and WeeFIM-SC, at most
332
post-treatment and follow-up time points. The hCIT group also performed better than the TR
333
group on the reach-to-grasp kinematics at post-treatment or the 3- and 6-month follow-ups,
334
demonstrating fewer nMUs, smaller MGA, shorter RTs, and shorter nMTs. That is, hCIT
335
induced greater temporal and spatial efficiencies of reach-to-grasp movements in children
336
with CP than TR in terms of increasing movement preplanning and execution, movement
337
smoothness, and hand grasping efficiency during both the immediate and maintenance phases.
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ACCEPTED MANUSCRIPT hCIT induced better motor control changes underlying greater functional improvement than
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TR in both the short- and long-term. The current study offers valuable kinematic biomarkers
340
that support the neural-motor models proposed to account for the hCIT effects on the
341
functional outcomes in children with CP. The kinematic parameters, particularly RT and nMU,
342
are the most useful for creating biomarkers to examine the benefits of CIT. The study results
343
are significant for translating kinematic measures into clinical effects from hCIT in children
344
with CP.
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hCIT generated greater gains in both the grasping skills (measured by PDMS-G) and
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daily activities (measured by WeeFIM-SC) at not only the post-treatment but also the
348
follow-ups than TR in children with CP. hCIT led to greater gains than TR in upper extremity
349
speed and dexterity (as measured by BOTMP-sub8) at the follow-ups, but not at
350
post-treatment. Enhanced motivation, repetition, shaping, persistence in exploring familiar
351
environments, and transfer package effects may be the reasons that the effects were
352
maintained after hCIT. A home environment also provides a rich natural context to facilitate
353
motivation and engagement using familiar objects in everyday functional activities.12, 16-17
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However, hCIT requires more time to induce upper extremity speed and dexterity changes.
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Previous studies have demonstrated that clinic-based CIT can lead to significant long-term
356
improvements in unimanual capacity, bimanual performance, and individualized outcomes
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ACCEPTED MANUSCRIPT 28-29
or across multiple functional performance measures.27 A previous follow-up RCT study
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also suggested that hCIT has beneficial effects on unilateral grasping skills and
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unilateral/bilateral functional performance at 6 months.13 The reinforced use of the more
360
affected upper extremity by constraining the less affected upper extremity decreases neglect
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of the more affected one, thereby reducing developmental disregard and improving upper
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extremity skills.4, 6 The improvement in upper extremity skills might further enhance the
363
functional performance and self-care activities in a child’s daily life.
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The beneficial effects of hCIT over TR leading to better motor control strategies were
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retained for 3–6 months. The hCIT group demonstrated shorter RTs and nMTs and fewer
367
nMUs at the follow-ups than the TR group. The enhanced control strategy after hCIT may be
368
a result of the intensive practice of the more affected upper extremity during functional tasks.
369
The most likely explanation for this retention is that learned non-use and use-dependent
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cortical re-organization39 is overcome through enhanced motor control strategies. Cortical
371
reorganization was maintained after CIT at the 6-month follow-up.40 Furthermore, the
372
resulting increase in the use of the more affected upper extremity may cause expansion of the
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contralateral cortical area controlling the movement of the more affected upper extremity and
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recruitment of new ipsilateral areas.39
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ACCEPTED MANUSCRIPT hCIT induced better temporal efficiency in terms of more preprogrammed and efficient
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movement execution strategies during both the short- and long-term phases than TR, as
378
shown by the shorter RTs and nMTs for reach-to-grasp tasks at post-treatment and the
379
follow-ups. Lin et al. also demonstrated that CIT induced more efficient preplanning of
380
reaching and grasping (shorter RTs) and a shift toward feed-forward control (a higher
381
percentage of movement time when peak velocity occurs) in patients with stroke compared
382
with TR.23 The improvement in the temporal efficiency is consistent with our findings of
383
better grasping skills and daily activities during both the short-term and long-term phases
384
after hCIT than after TR. The intensive practice for the more affected upper extremity
385
provided by CIT may provide sufficient proprioceptive and visual feedback to develop
386
internal models for feed-forward movement control23, 41-42 and learning effects for executing
387
movement with increased efficiency. Thus, motor control changes may help children with CP
388
learn to preplan motor patterns and execute motor tasks more efficiently after hCIT during
389
both the short- and long-term phases.
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hCIT induced better spatiotemporal efficiency by increasing the long-term rather than the
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short-term movement smoothness (fewer nMUs) during reach-to-grasp tasks. The reason for
393
this improvement may be that follow-up visits are long enough to detect the differences in the
394
movement smoothness between the 2 groups. The results are compatible with those in some
22
ACCEPTED MANUSCRIPT studies involving stroke patients9, 43 but are not consistent with those obtained by another
396
stroke study.23 The improvement in movement smoothness is consistent with our finding of
397
long-term rather than short-term enhanced movement speed and dexterity, as measured by
398
BOTMP, after hCIT compared with TR. The increase in movement smoothness indicates a
399
decreased amount of error correction,44-45 and movement increasingly depends on
400
feed-forward control.34, 46
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hCIT enhanced spatial efficiency in hand grasping (smaller MGA) during the
403
reach-to-grasp tasks at post-treatment, but not at the follow-ups, compared with TR. The
404
improvement in the spatial efficiency of hand grasping is partially consistent with our finding
405
of better grasping skills at both post-treatment and follow-ups compared with TR. The
406
findings that the long-term effects of hCIT can be detected in PDMS2 but not in MGA may be
407
explained by the following. The increased grasping skills at post-treatment can be maintained
408
at the follow-ups because the child had already developed these skills. However, the inability
409
to maintain the spatial efficiency of hand grasping that is enhanced at post-treatment may be
410
due to the lack of continuing intensive and repetitive training of the more affected upper
411
extremity. This finding is compatible with the results of a case report43 but is not consistent
412
with that of a RCT involving stroke patients.23 A hand opened widely may maximize the
413
likelihood of successfully grasping an object.37 Our results that children with CP achieved
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ACCEPTED MANUSCRIPT grasping movement without opening the hand widely following the hCIT indicate a
415
well-preplanned or skillful grasping movement.23, 37 The enhanced spatial efficiency in hand
416
grasping over the short-term after hCIT may be attributed to repeated functional practice and
417
shaping techniques for training the affected upper extremity.
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418
Both hCIT and TR therapy generated comparable performance in the online correction of
420
target grasping (measured by PMGA), which is compatible with a study of stroke patients.23In
421
combination with the results of MGA, our results suggest that the hCIT protocol was more
422
effective in promoting the child’s efficiency to perform hand opening while grasping a ball
423
but not in promoting online correction during hand transportation. A possible explanation is
424
that the accuracy demands of the grasp-a-ball task were relatively low as the ball is stationary
425
and the round shape is familiar to the children.23 The PMGA indicates the online correction
426
(temporal efficiency) during hand transportation, which may be related to the accuracy
427
demands of the task. However, the MGA indicates the spatial efficiency of hand grasping,
428
which may be related to the child’s ability to perform wrist and finger extension during grip
429
formation. Children with CP may preserve the ability to grasp a familiar target with little
430
online correction of hand posture during hand enclosure.23, 47-48 Thus, the grasp-a-ball task
431
may be too simple to detect between-group PMGA differences after the interventions. The use
432
of differently sized objects or unfamiliar objects may be more applicable for differentiating
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ACCEPTED MANUSCRIPT 433
between possible changes after treatment.
434 Children in both groups performed comparably with respect to force control (measured
436
by PV) during the reach-to-grasp task immediately after the intervention and during the
437
follow-ups. A high PV amplitude indicates a high force produced at movement initiation and
438
good force control while reaching toward a target.45, 49 The non-significant differences for PV
439
amplitude between the two interventions may be because hCIT did not focus on force
440
production or control training.
441
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The strength of this study protocol is the home-based intervention implemented by a
443
therapist. Home-based interventions have advantages over clinic-based interventions.
444
Compared with the clinic-based group, the home-based group showed significant
445
improvement in motor proficiency and functional performance after CIT in the follow-up
446
sessions.14 The hCIT may transfer greater training effects to daily life and induce greater
447
‘transfer package’ effects than clinic-based CIT. The transfer package allows children to
448
transfer the treatment gains to real-world activities.8 In combination with the home
449
environment, hCIT facilitates the learning processes,16 enhances daily function,23 promotes
450
family participation, generalizes certain therapeutic events to a child’s daily activities, and
451
increases the adherence of parents and therapists.50 The home-based intervention may also
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ACCEPTED MANUSCRIPT facilitate the development of exploratory behavior in children as the parents serve as a secure
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base for exploration.51-52 In addition, this study provided the same treatment dosage and
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one-on-one therapy sessions at home for both groups. This study design may reduce bias from
455
different treatment dosages and enhance hCIT treatment effects in natural environments for
456
children with CP.
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Considering the practical feasibility and compliance of the children and caregivers, we
459
chose 3.5–4 hours/day for the restraint of the more affected upper extremity with a mitten. A
460
systemic review indicated the restraint time and treatment frequency of CIT in children with
461
CP varied among studies.9 The intervention time for pediatric CIT varied from 1 hour per
462
week to 7 hours per day for 4 weeks to 8 months. Most school children with hemiplegia could
463
not write or complete homework after school with the more affected upper extremity. School
464
children often had 6-8 free hours after school. Therefore, this study designated 3.5-4 hours for
465
intensive training and shaping of the more affected upper extremity with restraint of the less
466
affected one. The children were allowed 1-3 hours for their school work with the less affected
467
upper extremity. In addition, the mitten, rather than splinting or a univalved or bivalved cast,
468
was selected as a restraint to enhance the compliance as it is more convenient, lighter, and
469
easier to use.
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ACCEPTED MANUSCRIPT 471 472
Study Limitations Several study limitations should be considered. The inclusion criteria included mild to
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moderate impairment of upper limb function. Children with severely impaired upper limb
475
function were not included. Thus, the study results cannot be generalized to all children with
476
CP. Using a uniform, familiar object (a ball) as the grasping target to assess treatment efficacy
477
may be another limitation. Using smaller objects than that used in this study may increase the
478
sensitivity for differentiating between possible changes after treatment. Despite these
479
limitations, this study demonstrates the beneficial effects of hCIT on motor control strategies
480
and functional changes relative to those of TR.
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CONCLUSION
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hCIT induced better spatial and temporal control strategies underlying functional
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improvement than TR. hCIT generated smoother movement, more efficient hand grasping,
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and better movement preplanning and execution than TR. Furthermore, the beneficial effects
487
on the motor control strategies, upper limb efficacy, and functional outcomes were maintained
488
up to 6 months after the treatment.
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ACCEPTED MANUSCRIPT Figure Legends
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Figure 1. Flow diagram of the randomization procedure.
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Figure 2. The setup of the reach-to-grasp kinematic task (Trunk restraint is not shown).
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ACCEPTED MANUSCRIPT Table 1. Demographic and baseline characteristics of both groups
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Variables hCIT (n=23) TR (n=22) p value Age, years 8.73 (1.9) 8.66 (2.0) 0.909a Sex Boys 11 [48] 10 [46] 0.873b Girls 12 [52] 12 [54] More affected arm Right 12 [52] 11 [52] 0.884b Left 11 [48] 11 [48] BFMF Level I 3 [13] 3 [14] 0.953 b Level II 20 [87] 19 [86] Reach-to-grasp kinematics RT 0.57 (0.01) 0.57 (0.01) 0.954 a nMT 0.61 (0.05) 0.63 (0.03) 0.081 a nMU 0.29 (0.03) 0.27 (0.03) 0.037 a PV 65.11 (6.09) 65.16 (3.14) 0.953 a MGA 9.38 (0.95) 9.39 (0.88) 0.955 a PMGA 74.81 (18.93) 88.69 (13.24) 0.007 a PDMS-2 Grasping 39.65 (2.95) 38.73 (2.68) 0.277 a BOTMP Sub-8 4.91 (1.35) 4.64 (1.14) 0.461 a WeeFIM Self-care 39.57 (6.33) 37.41 (3.67) 0.169 a Values are expressed as mean (SD) or n [%]; a t tests; b chi-square tests. hCIT, home-based constraint-induced therapy; TR, traditional rehabilitation; BFMF, bimanual fine motor function; RT, reaction time; nMT, normalized movement time; nMU, normalized number of movement unit; PV, peak velocity; MGA, maximum grip aperture; PMGA, percent time where maximum grip aperture occurs; PDMS-2, Peabody Developmental Motor Scales-2; BOTMP, Bruininks-Oseretsky Test of Motor Proficiency; WeeFIM, Functional Independence Measure for Children.
ACCEPTED MANUSCRIPT
BOTMP Sub-8
hCIT (n=23)
TR (n=22)
43.96 (2.72)
41.27 (3.27)
8.87 (2.26)
7.86 (1.64)
hCIT (n=23)
TR (n=22)
61.15
S0003-9993(14)00266-4
DOI:
10.1016/j.apmr.2014.03.025
Reference:
YAPMR 55796
To appear in:
ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
Received Date: 18 August 2013 Revised Date:
17 March 2014
Accepted Date: 27 March 2014
Please cite this article as: Chen H-c, Chen C-l, Kang L-j, Wu C-y, Chen F-c, Hong W-h, Improvement of upper extremity motor control and function after home-based constraint-induced therapy in children with unilateral cerebral palsy: Immediate and long-term effects, ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION (2014), doi: 10.1016/j.apmr.2014.03.025. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Running head: Motor Control and Constraint-Induced Therapy in CP
Improvement of upper extremity motor control and function after home-based
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constraint-induced therapy in children with unilateral cerebral palsy: Immediate and
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long-term effects
Hsieh-ching Chen,a* PhD; Chia-ling Chen,b,c* MD, PhD; Lin-ju Kang,c PhD; Ching-yi Wu,d
a
Hsieh-ching Chen and Chia-ling Chen contributed equally to this manuscript.
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*
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ScD, OTR; Fei-chun Chen,c,e MS, Wei-hsien Hong,f PhD
Department of Industrial Engineering & Management, National Taipei University of
Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital,
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Technology, 1 Chung-hsiao E. Rd., Sec. 3, Taipei 106, Taiwan
Linkou, 5 Fu-Hsing St., Kwei-Shan, Tao-Yuan 333, Taiwan c
Graduate Institute of Early Intervention, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Rd., Kwei-Shan, Tao-Yuan 333, Taiwan
d
Graduate Institute of Behavioral Sciences and Dept. of Occupational Therapy, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Rd., Kwei-Shan, Tao-Yuan 333, Taiwan
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Buddhist Tzu Chi General Hospital, 289 Jianguo Rd., Xindian, New Taipei City 231, Taiwan
f
Department of Sports Medicine, China Medical University, 91 Hsueh-Shih Rd., Taichung
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40402, Taiwan
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To whom correspondence, proofs and reprints requests should be made:
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Chia-ling Chen, MD, PhD Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Linkou
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5 Fu-hsing St., Kwei-shan, Tao-yuan 333, Taiwan E-mail: [email protected]
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Word counts: main text- 4,862 words; Abstract- 274 words
Source of support: the National Science Council [NSC 102-2410-H-182-018, NSC 101-2314-B-182-004-MY3] and Chang Gung Medical Foundation [CMRPG 391671-3] in Taiwan.
Financial disclosure: We certify that no party having a direct interest in the results of the
ACCEPTED MANUSCRIPT research supporting this article has or will confer a benefit on us or on any organization with which we are associated AND, we certify that all financial and material support for this
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research and work are clearly identified in the title page of the manuscript.
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Clinical trial registration number: ClinicalTrials.gov ID No. NCT01076257
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Acknowledgments: The authors would like to thank the National Science Council [NSC 102-2410-H-182-018, NSC 101-2314-B-182-004-MY3] and Chang Gung Medical Foundation [CMRPG 391671-3] for financially support. Ted Knoy is appreciated for his
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editorial assistance.
ACCEPTED MANUSCRIPT Improvement of upper extremity motor control and function after home-based
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constraint-induced therapy in children with unilateral cerebral palsy: Immediate and
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long-term effects
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ACCEPTED MANUSCRIPT Abstract
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Objective: To investigate the long-term effects of home-based constraint-induced therapy
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(hCIT) on motor control underlying functional change in children with unilateral cerebral
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palsy (CP).
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Design: A randomized controlled trial.
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Setting: Home-based.
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Participants: Forty-five children with unilateral CP (aged 6–12 years) were randomly
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assigned to receive hCIT (n = 23) or traditional rehabilitation (TR) (n = 22).
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Interventions: Both groups received a 4-week therapist-based intervention at home. The
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hCIT involved intensive functional training of the more affected upper extremity while the
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less affected one was restrained. The TR involved functional unimanual and bimanual
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training.
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Main Outcome Measures: All children underwent kinematic and clinical assessments at
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baseline, 4 weeks (post-treatment), and 3 and 6 months (follow-up). The reach-to-grasp
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kinematics were reaction time (RT), normalized movement time (nMT), normalized
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movement unit (nMU), peak velocity (PV), maximum grip aperture (MGA), and percentage
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of movement where MGA occurs (PMGA). The clinical measures were the Peabody
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Developmental Motor Scale 2 (PDMS-2), Bruininks-Oseretsky Test of Motor Proficiency
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(BOTMP), and Functional Independence Measure for children (WeeFIM).
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ACCEPTED MANUSCRIPT Results: The hCIT group showed a shorter RT (p < 0.050) and nMT (p < 0.010), smaller
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MGA (p = 0.006), and fewer nMU (p = 0.014) in the reach-to-grasp movements at
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post-treatment and follow-up than the TR group. The hCIT group improved more on the
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PDMS-2 (p < 0.001) and the WeeFIM (p < 0.010) in all post-treatment tests and on the
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BOTMP (p < 0.010) at follow-up than the TR group.
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Conclusions: The hCIT induced better spatial and temporal efficiency (smoother movement,
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more efficient grasping, and better movement preplanning and execution) for functional
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improvement up to 6 months after treatment than the TR.
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Key Words: Cerebral palsy; Constraint-induced therapy; Kinematic analysis; Functional
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outcome; Randomized controlled trial
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CP, cerebral palsy
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CIT, constraint-induced therapy
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hCIT, home-based constraint-induced therapy
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PDMS-2, Peabody Developmental Motor Scale–2nd edition
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PDMS-G, Peabody Developmental Motor Scales-grasping subscale
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PDMS-VMI, Peabody Developmental Motor Scales-visual motor integration subscale
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BOTMP, Bruininks-Oseretsky Test of Motor Proficiency
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WeeFIM, Functional Independence Measure for Children
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WeeFIM-SC, Functional Independence Measure for Children -self-care subscale
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RT, reaction time
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nMT, normalized movement time
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nMU, normalized movement unit
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PV, peak velocity
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MGA, maximum grip aperture
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PMGA, percentage of movement where MGA occurs
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Cerebral palsy (CP) is a major childhood disability.1 The motor disorders of CP are often associated
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sensation,
perception,
cognition,
communication,
behavior,
and
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musculoskeletal problems.2 Children with unilateral or hemiparetic CP often present with
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unilateral spasticity, weakness, early asymmetry in movements and/or functional abilities (i.e.,
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asymmetrical crawl or early hand preference), and a high rate of partial seizures.1 The upper
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extremities are often more involved than the lower extremities in children with unilateral CP.2
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Children with unilateral CP typically learn strategies and techniques to perform daily tasks
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with one hand.3 Children with unilateral CP typically do not use their more affected upper
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extremity. They frequently use their less affected upper extremity to increase the efficiency of
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performing tasks, which is called developmental disregard.3-5 These problems further limit the
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daily activities and participation of children with unilateral CP.
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Constraint-induced therapy (CIT) is an intervention approach for treating developmental
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disregard in patients with unilateral motor involvement.6-7 CIT involves intensive functional
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training and shaping for the more affected upper extremity, a constraint for the less affected
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upper extremity, and a behavioral technique termed 'transfer package'.6, 8 The component of
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the ‘transfer package’ in CIT could facilitate turning the therapeutic gains achieved in the
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clinic into real-world activities and retention of the treatment effects 6 months later.8 The aim
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of CIT is to reverse the behavioral suppression of the movement of the more affected upper
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extremity.3 Several systematic review studies3, 7, 9 and randomized controlled trials (RCTs)4, 6,
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10-13
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living in children with CP.
have demonstrated that CIT improves the functional performance and activities of daily
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Home-based CIT (hCIT) places the practice in a natural context and is the preferred
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method for the treatment of children with CP over clinic-based CIT.14 A home environment
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can enhance motivation, engagement, and repetition in everyday activities for children.15-17
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Home-based therapy can facilitate the transfer of the training effects of CIT to daily life 18 and
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may also enhance greater ‘transfer package’ effects than clinic-based CIT. Furthermore, the
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hCIT protocol, with its relatively moderate intensity and shortened constraint time, might
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balance the effectiveness and compliance of the children and caregivers.13, 19-20 Therefore,
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hCIT may be an effective alternative to conventional CIT.13, 19-20
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Therapies for upper extremity dysfunction in children with CP typically target functional
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outcomes and underlying motor control impairments. Kinematic analysis can reveal the motor
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control strategies underlying the performance of motor tasks. Reach and reach-to-grasp are
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fundamental motor tasks that a child needs to interact with his surrounding environment in
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daily living. The kinematic parameters of a reach task, such as reaction time (RT), normalized
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movement time (nMT), and normalized movement units (nMUs), can provide information on
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reach-to-grasp task can provide additional information on grip formation, such as the
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maximum grip aperture (MGA) and the percentage of movement time during which
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maximum grip aperture (PMGA) occurs. High efficiency of a reach-to-grasp task is
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characterized by a short RT and nMT (movement preplanning and execution), few nMUs
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(increased movement smoothness), a small MGA (minimal hand opening while grasping),
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and a high PMGA.23 Research has demonstrated that CIT produces a greater improvement in
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motor control on reaching or reach-to-grasp tasks and functional performance in stroke
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patients than traditional rehabilitation (TR) therapy.21-23 In this study, the RT, nMT, nMU,
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MGA, and PMGA were selected for kinematic analysis because these parameters indicate the
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ability to complete the functional tasks smoothly and efficiently.20-23
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Previously we compared hCIT with TR and examined the effects of hCIT on the motor
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performance of children with CP over different time frames. Subsets of data from this study
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have been published in our previous two manuscripts.19-20 In the first manuscript,19 we used
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only those children from this data set who were 6-8 years of age and compared the
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effectiveness of hCIT with TR
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Developmental Motor Scale-2nd edition (PDMS-2)24 and the Pediatric Motor Activity Log
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(PMAL)25 were selected as the main functional outcome measures. We found that hCIT
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at post-treatment and at 3-month follow-up. The Peabody
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at both times. In the second manuscript,20 we used all children from this data set and focused
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on examining the effects of hCIT on reaching kinematics by using a simple reach task at
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post-treatment, but not at follow-ups. The Bruininks-Oseretsky Test of Motor Proficiency
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(BOTMP)26 and PMAL were used as the main functional outcome measures.20 We found that
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hCIT induced greater temporal and spatiotemporal efficiency in the short term, as
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demonstrated by shorter RT and nMT and higher peak velocity (PV) compared with TR.20
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However, there have been no studies investigating the long-term changes in motor control
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strategies after CIT in children with CP using a more complex reach-to-grasp task (e.g., reach
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and grasp a ball or can) rather than a simple reach task (e.g., reach and press a bell or button).
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The long-term effects of either CIT27-29 or hCIT13, 19 on the motor function of children
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with CP have already been established. To the best of our knowledge, the long-term effects of
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hCIT on the motor control strategies of children with CP have not yet been elucidated.
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Therefore, the current study is a follow-up RCT to our two previous studies.19-20 We compared
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both the immediate (post-treatment) and maintained (3-month and 6-month) effects of hCIT
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and TR therapy by combining the kinematic analysis of a reach-to-grasp task and clinical
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evaluations. We will determine whether functional improvement is accompanied by changes
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in motor control in both short- and long-term time frames. For this study, the
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as the primary outcome measures. The Functional Independence Measure for Children
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(WeeFIM)30 was used as the secondary outcome measure. The rationale for using
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dose-matched interventions for both groups is based on RCTs of CP13,19-20 and stroke.21-23 We
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hypothesized that hCIT would generate greater functional gains accompanied by better motor
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control strategies (shorter RT and nMT, fewer nMUs, smaller MGA and PMGA, and larger
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PV) of reach-to-grasp than TR in both the immediate phase (at post-treatment) and the
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maintenance phase (at 3- and 6-month follow-ups). The study findings will help clinicians
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elucidate the neuro-motor control strategies underlying functional improvement after hCIT.
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METHODS
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Participants
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Children with CP aged 6–12 years from the Department of Physical Medicine and
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Rehabilitation of a tertiary medical center were recruited for this study. The
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inclusion/exclusion criteria were reported in our previous manuscript.20 Briefly, the inclusion
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criteria included a diagnosis of congenital unilateral spastic CP, considerable nonuse of the
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more affected upper extremity, active extension movement of the wrist and metaphalangeal
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joint ≥ 10°, and no excessive muscle tone of the more affected upper extremity. The exclusion
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not typically associated with CP, active medical conditions, and any major surgery or nerve
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blockage in the previous 6 months prior to the exposure to CIT. Ethical approval was
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provided by the Institutional Review Board for Human Studies of Chang Gung Memorial
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Hospital (No. 97-1823B) and registered under ClinicalTrials.gov ID No. NCT01076257.
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Caregivers of all participants gave written informed consent.
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Design
This was a single-blinded randomized controlled trial (Figure 1) as reported in our two previous manuscripts.19-20 All children who participated in the study were randomly assigned
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to either the hCIT or the TR group. Among the 75 eligible candidates, a total of 45 children
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with spastic unilateral CP (23 in the hCIT group and 22 in the TR group) were included in the
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final analysis. Children were first stratified by age into two strata (6–8 years and 9–12 years).
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The cut-off age was 8 as the fine finger force coordination in children grasping objects
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approximated that of adults by 8 years old.31-32
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The randomization procedure was reported in our previous manuscript.20 Each age strata
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had a set of sealed envelopes to facilitate the randomized allocation of 45 children into either
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the hCIT or TR groups. There were two sets of envelopes in total, and each set contained 30
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sealed envelopes labeled from 1 to 30 with a group allocation (hCIT or TR).
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measures (primary and secondary outcomes) in a laboratory setting before the intervention
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(pretreatment). An occupational therapist blinded to the group assignment was trained to
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administer these outcome measures. All children underwent these assessments again at 4
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weeks immediately after the intervention (post-treatment), at a 3-month follow-up, and at a
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6-month follow-up. The children’s demographic characteristics, the more affected upper
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extremity, the level of bimanual fine motor function (BFMF),33 and the constraint time (in the
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hCIT group only) were recorded.
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Details of the interventions have been described in our previous manuscript.20 Both
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groups received individualized home-based interventions of 3.5–4 hours/day, twice weekly
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for 4 weeks. One certified physical therapist provided treatments to all the children. The hCIT
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approach adopted in this study may reduce the treatment dosage and constraint time needed to
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achieve benefits by enhancing participant compliance.19-20 The hCIT program focused on the
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and repetitive task practice. Children in the hCIT group were required to wear an elastic
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bandage and a restraint mitten on the less affected upper extremity for 3.5–4 hours/day for 4
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weeks, and their parents were asked to document the number of restraint hours. Children in
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the TR group were engaged in functional unilateral or bilateral upper extremity training using
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the principles of an activity-oriented approach, neurodevelopment treatment techniques, and
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motor learning and control. Both groups continued their usual clinic-based rehabilitation
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programs. Between treatment sessions, children in both groups were encouraged to exercise
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or perform daily activities under parental supervision, such as reaching or grasping objects,
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manipulating their own toys, eating, writing, drawing, and tool usage. Children in hCIT group
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were encouraged to exercise or perform daily functional activities with the more affected
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upper limb, while those in TR group performed daily activities with unilateral or bilateral
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upper limbs.
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Outcome Measures
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Primary outcomes
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Subtest 8 of the BOTMP (BOTMP-sub8),26 which includes 8 items, was used to evaluate
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upper extremity speed and dexterity. Subtest 8 assesses the ability of the child to move and
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such as placing pennies, sorting cards, stringing beads, displacing pegs, drawing lines, and
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marking dots.26 The BOTMP-sub8 was selected because this subtest measures upper
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extremity speed and dexterity during a variety of reach-to-pinch and hand manipulating
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movements. The unimanual tasks on the BOTMP were measured with the more affected
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upper extremity.
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The fine motor domain of the PDMS-2 was used to assess upper extremity functional
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ability.24 The grasping subscale (PDMS-G), which includes 26 items, was selected to assess
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grasping, releasing, and manipulating skills. Unimanual tasks were performed with the more
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affected upper extremity. The BOTMP and PDMS-2, in which higher raw scores indicate
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better performance, have well-established psychometric properties for the total scale and for
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each subscale in children with motor disabilities.24, 26 The PDMS-G was selected because it
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measures functional grasping skills that correspond to the reach-to-grasp kinematic task.
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Secondary outcomes
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The WeeFIM30 includes three functional subscales: self-care, mobility, and cognition.
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The level of independence is rated by a 7-level ordinal rating system ranging from 7
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(complete independence) to 1 (total assistance). The self-care subscale (WeeFIM-SC), which
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pertains to upper limb functions, was selected to measure the performance in daily activities.
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The responsiveness of the WeeFIM instrument has been shown to document changes in the
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functional abilities of children with chronic developmental disabilities.30
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Details of the experimental set-ups for the kinematic analyses have been described in our
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previous manuscript.20 During the reach-to-grasp task (Figure 2), the child sat on a chair
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adjacent to a table with his/her trunk secured to the chair by a harness. The child rested the
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affected hand on a pressure-sensitive hand switch located in line with the child’s affected side.
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A ball 8 cm in diameter was positioned along the child’s midsagittal plane. The distance to
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reach the ball was standardized to the child’s arm length. If the maximum distance the child
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could reach was less than his/her arm length, the distance to reach the ball was adjusted to the
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maximum reachable distance. The child was instructed to reach, grasp, and lift the ball at
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his/her own speed. A start signal was used to start the task.
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Reference markers were placed on the distal interphalangeal joints of the thumb and
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index finger, the styloid process of the ulna, the proximal end of the second metacarpal at the
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base of the 2nd finger, and the ball. An eight-camera motion analysis system (Vicon MX 3-D;
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Oxford Metrics Inc., Oxford, UK) was used to capture the movement of these reference
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connected to the hand switch was used to identify movement onset. The reference marker
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attached to the ball was used to determine movement offset. Movement recording began when
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the child’s hand moved off of the switch and terminated when the marker attached to the ball
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moved.23
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Data Reduction and Data Analysis
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The kinematic data from the reach-to-grasp movements were processed by an analytical
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program coded in LabVIEW (National Instruments Corp., Austin, TX, USA). The parameters
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were as follows: RT, nMT, nMUs, PV, MGA, and PMGA.23 The RT is the interval from the
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start signal to movement onset,34 MT is the interval between movement onset and movement
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completion (i.e., lifting the ball),23, 35-36 and MU is used to characterize movement smoothness
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and the control strategy of reaching that is extracted from the ulnar styloid data. One MU
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comprises one acceleration phase and one deceleration phase. Normalization of MT and MU
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was performed to adjust for differences in reaching distance.23 PV is defined as the highest
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instantaneous velocity during the movement. MGA, a measure of the extent of hand opening,
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was defined as the maximum distance between the thumb and index finger. PMGA, in which
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maximum grip aperture occurs, is a measure of the online correction of target grasping during
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online correction of target grasping.37 A small MGA indicates greater spatial efficiency due to
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less hand opening needed for grasping objects.37 A small MGA is often considered to be
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better because the child can grasp the objects with a relatively small aperture.
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Statistical Analysis
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All statistical analyses were conducted using the SPSS 12.0 software (SPSS, Inc.,
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Chicago, IL, USA). To determine the comparability of the demographic and clinical
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characteristics at baseline, an independent two-sample t-test was applied for continuous
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variables, and a chi-square test was applied for categorical variables. Analysis of covariance
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(ANCOVA), while controlling for pretest differences, was used to determine whether the
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hCIT group performed significantly better than the TR group for each outcome variable
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(reach-to-grasp kinematics and scores for the PDMS-2, BOTMP, and WeeFIM). During each
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analysis, the pretest performance was controlled as a covariate, the group was the independent
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variable, and the post-treatment performance was the dependent variable. The significance
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level was set to 0.050. The effect size, η2, was calculated for each outcome variable to reflect
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the magnitude of the between-group differences. A large effect is represented by an η2 of at
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least 0.138, a moderate effect by an η2 of 0.059, and a small effect by an η2 of 0.010.38
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RESULTS Among the 48 children who initially participated in this study, one child in the TR group
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was unable to complete the follow-up due to a tight family schedule and lack of transportation
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to the site of the posttest assessments (Figure 1). One child in each of the hCIT and TR groups
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was excluded from the analysis because their motor ability was insufficient to complete the
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standardized study procedure of the reach-to-grasp kinematic analysis. Consequently, a total
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of 45 children, 23 in the hCIT group and 22 in the TR group, completed the intervention,
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posttest, and follow-up measures.
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Demographic and Baseline Characteristics
The demographic characteristics of these two groups were comparable (Table 1). The
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pretest results indicated that no differences existed between the two groups in the scores for
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functional measures and reach-to-grasp kinematics, except for the nMU and PMGA scores.
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The hCIT group had greater nMUs and lower PMGAs than the TR group (p = 0.007–0.037).
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Primary Outcomes The PDMS-G and BOTMP-sub8 scores at all post-treatment times for both groups were
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improved more than the TR group on the PDMS-G at not only the post-treatment but also
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both follow-ups (3 and 6 months), with large effects (η2 = 0.604–0.658, p < 0.001).
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Furthermore, the hCIT group has also shown greater improvement than the TR group on the
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BOTMP-sub8 at the 3- and 6-month follow-ups, with large effects (η2 = 0.167–0.193, p =
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0.003–0.006), but not at post-treatment.
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For the daily activity assessments, the WeeFIM-SC scores for both groups improved at
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not only the post-treatment but also both follow-ups (Table 2). The ANCOVA results
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indicated that the hCIT group improved more than the TR group on the WeeFIM-SC at
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post-treatment and both follow-ups, with large effects (η2 = 0.195–0.264, p < 0.001 to p =
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0.003).
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Reach-to-grasp Kinematics
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Both groups had improved reach-to-grasp kinematics at both post-treatment and the
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follow-ups (Table 3). Relative to the TR group, the hCIT group improved more in RT (η2 =
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0.133–0.221, p = 0.001–0.015) and nMT (η2 = 0.158–0.601, p < 0.001 to p = 0.008) at both
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the post-treatment and the follow-ups, with large effects. Additionally, the hCIT group
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moderate effect (η2 = 0.136, p = 0.014), but not at post-treatment or the 3-month follow-up.
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Moreover, the hCIT group improved more than the TR group with respect to MGA at
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post-treatment, with a large effect (η2 = 0.169, p = 0.006), but not at the 3- and 6-month
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follow-ups. The PV and PMGA scores did not differ between the two groups.
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This study is the first, to the best of our knowledge, to reveal the long-term effects of
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hCIT on motor control strategies by using reach-to-grasp kinematics in combination with
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functional improvement in children with CP. Other related studies usually focused only on
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functional improvement. Compared with TR, the hCIT group improved more on the
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functional outcomes, as measured by the PDMS-G, BOTMP-sub8, and WeeFIM-SC, at most
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post-treatment and follow-up time points. The hCIT group also performed better than the TR
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group on the reach-to-grasp kinematics at post-treatment or the 3- and 6-month follow-ups,
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demonstrating fewer nMUs, smaller MGA, shorter RTs, and shorter nMTs. That is, hCIT
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induced greater temporal and spatial efficiencies of reach-to-grasp movements in children
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with CP than TR in terms of increasing movement preplanning and execution, movement
337
smoothness, and hand grasping efficiency during both the immediate and maintenance phases.
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ACCEPTED MANUSCRIPT hCIT induced better motor control changes underlying greater functional improvement than
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TR in both the short- and long-term. The current study offers valuable kinematic biomarkers
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that support the neural-motor models proposed to account for the hCIT effects on the
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functional outcomes in children with CP. The kinematic parameters, particularly RT and nMU,
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are the most useful for creating biomarkers to examine the benefits of CIT. The study results
343
are significant for translating kinematic measures into clinical effects from hCIT in children
344
with CP.
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hCIT generated greater gains in both the grasping skills (measured by PDMS-G) and
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daily activities (measured by WeeFIM-SC) at not only the post-treatment but also the
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follow-ups than TR in children with CP. hCIT led to greater gains than TR in upper extremity
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speed and dexterity (as measured by BOTMP-sub8) at the follow-ups, but not at
350
post-treatment. Enhanced motivation, repetition, shaping, persistence in exploring familiar
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environments, and transfer package effects may be the reasons that the effects were
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maintained after hCIT. A home environment also provides a rich natural context to facilitate
353
motivation and engagement using familiar objects in everyday functional activities.12, 16-17
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However, hCIT requires more time to induce upper extremity speed and dexterity changes.
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Previous studies have demonstrated that clinic-based CIT can lead to significant long-term
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improvements in unimanual capacity, bimanual performance, and individualized outcomes
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ACCEPTED MANUSCRIPT 28-29
or across multiple functional performance measures.27 A previous follow-up RCT study
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also suggested that hCIT has beneficial effects on unilateral grasping skills and
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unilateral/bilateral functional performance at 6 months.13 The reinforced use of the more
360
affected upper extremity by constraining the less affected upper extremity decreases neglect
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of the more affected one, thereby reducing developmental disregard and improving upper
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extremity skills.4, 6 The improvement in upper extremity skills might further enhance the
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functional performance and self-care activities in a child’s daily life.
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The beneficial effects of hCIT over TR leading to better motor control strategies were
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retained for 3–6 months. The hCIT group demonstrated shorter RTs and nMTs and fewer
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nMUs at the follow-ups than the TR group. The enhanced control strategy after hCIT may be
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a result of the intensive practice of the more affected upper extremity during functional tasks.
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The most likely explanation for this retention is that learned non-use and use-dependent
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cortical re-organization39 is overcome through enhanced motor control strategies. Cortical
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reorganization was maintained after CIT at the 6-month follow-up.40 Furthermore, the
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resulting increase in the use of the more affected upper extremity may cause expansion of the
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contralateral cortical area controlling the movement of the more affected upper extremity and
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recruitment of new ipsilateral areas.39
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ACCEPTED MANUSCRIPT hCIT induced better temporal efficiency in terms of more preprogrammed and efficient
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movement execution strategies during both the short- and long-term phases than TR, as
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shown by the shorter RTs and nMTs for reach-to-grasp tasks at post-treatment and the
379
follow-ups. Lin et al. also demonstrated that CIT induced more efficient preplanning of
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reaching and grasping (shorter RTs) and a shift toward feed-forward control (a higher
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percentage of movement time when peak velocity occurs) in patients with stroke compared
382
with TR.23 The improvement in the temporal efficiency is consistent with our findings of
383
better grasping skills and daily activities during both the short-term and long-term phases
384
after hCIT than after TR. The intensive practice for the more affected upper extremity
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provided by CIT may provide sufficient proprioceptive and visual feedback to develop
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internal models for feed-forward movement control23, 41-42 and learning effects for executing
387
movement with increased efficiency. Thus, motor control changes may help children with CP
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learn to preplan motor patterns and execute motor tasks more efficiently after hCIT during
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both the short- and long-term phases.
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hCIT induced better spatiotemporal efficiency by increasing the long-term rather than the
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short-term movement smoothness (fewer nMUs) during reach-to-grasp tasks. The reason for
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this improvement may be that follow-up visits are long enough to detect the differences in the
394
movement smoothness between the 2 groups. The results are compatible with those in some
22
ACCEPTED MANUSCRIPT studies involving stroke patients9, 43 but are not consistent with those obtained by another
396
stroke study.23 The improvement in movement smoothness is consistent with our finding of
397
long-term rather than short-term enhanced movement speed and dexterity, as measured by
398
BOTMP, after hCIT compared with TR. The increase in movement smoothness indicates a
399
decreased amount of error correction,44-45 and movement increasingly depends on
400
feed-forward control.34, 46
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hCIT enhanced spatial efficiency in hand grasping (smaller MGA) during the
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reach-to-grasp tasks at post-treatment, but not at the follow-ups, compared with TR. The
404
improvement in the spatial efficiency of hand grasping is partially consistent with our finding
405
of better grasping skills at both post-treatment and follow-ups compared with TR. The
406
findings that the long-term effects of hCIT can be detected in PDMS2 but not in MGA may be
407
explained by the following. The increased grasping skills at post-treatment can be maintained
408
at the follow-ups because the child had already developed these skills. However, the inability
409
to maintain the spatial efficiency of hand grasping that is enhanced at post-treatment may be
410
due to the lack of continuing intensive and repetitive training of the more affected upper
411
extremity. This finding is compatible with the results of a case report43 but is not consistent
412
with that of a RCT involving stroke patients.23 A hand opened widely may maximize the
413
likelihood of successfully grasping an object.37 Our results that children with CP achieved
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ACCEPTED MANUSCRIPT grasping movement without opening the hand widely following the hCIT indicate a
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well-preplanned or skillful grasping movement.23, 37 The enhanced spatial efficiency in hand
416
grasping over the short-term after hCIT may be attributed to repeated functional practice and
417
shaping techniques for training the affected upper extremity.
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Both hCIT and TR therapy generated comparable performance in the online correction of
420
target grasping (measured by PMGA), which is compatible with a study of stroke patients.23In
421
combination with the results of MGA, our results suggest that the hCIT protocol was more
422
effective in promoting the child’s efficiency to perform hand opening while grasping a ball
423
but not in promoting online correction during hand transportation. A possible explanation is
424
that the accuracy demands of the grasp-a-ball task were relatively low as the ball is stationary
425
and the round shape is familiar to the children.23 The PMGA indicates the online correction
426
(temporal efficiency) during hand transportation, which may be related to the accuracy
427
demands of the task. However, the MGA indicates the spatial efficiency of hand grasping,
428
which may be related to the child’s ability to perform wrist and finger extension during grip
429
formation. Children with CP may preserve the ability to grasp a familiar target with little
430
online correction of hand posture during hand enclosure.23, 47-48 Thus, the grasp-a-ball task
431
may be too simple to detect between-group PMGA differences after the interventions. The use
432
of differently sized objects or unfamiliar objects may be more applicable for differentiating
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ACCEPTED MANUSCRIPT 433
between possible changes after treatment.
434 Children in both groups performed comparably with respect to force control (measured
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by PV) during the reach-to-grasp task immediately after the intervention and during the
437
follow-ups. A high PV amplitude indicates a high force produced at movement initiation and
438
good force control while reaching toward a target.45, 49 The non-significant differences for PV
439
amplitude between the two interventions may be because hCIT did not focus on force
440
production or control training.
441
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The strength of this study protocol is the home-based intervention implemented by a
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therapist. Home-based interventions have advantages over clinic-based interventions.
444
Compared with the clinic-based group, the home-based group showed significant
445
improvement in motor proficiency and functional performance after CIT in the follow-up
446
sessions.14 The hCIT may transfer greater training effects to daily life and induce greater
447
‘transfer package’ effects than clinic-based CIT. The transfer package allows children to
448
transfer the treatment gains to real-world activities.8 In combination with the home
449
environment, hCIT facilitates the learning processes,16 enhances daily function,23 promotes
450
family participation, generalizes certain therapeutic events to a child’s daily activities, and
451
increases the adherence of parents and therapists.50 The home-based intervention may also
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ACCEPTED MANUSCRIPT facilitate the development of exploratory behavior in children as the parents serve as a secure
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base for exploration.51-52 In addition, this study provided the same treatment dosage and
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one-on-one therapy sessions at home for both groups. This study design may reduce bias from
455
different treatment dosages and enhance hCIT treatment effects in natural environments for
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children with CP.
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Considering the practical feasibility and compliance of the children and caregivers, we
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chose 3.5–4 hours/day for the restraint of the more affected upper extremity with a mitten. A
460
systemic review indicated the restraint time and treatment frequency of CIT in children with
461
CP varied among studies.9 The intervention time for pediatric CIT varied from 1 hour per
462
week to 7 hours per day for 4 weeks to 8 months. Most school children with hemiplegia could
463
not write or complete homework after school with the more affected upper extremity. School
464
children often had 6-8 free hours after school. Therefore, this study designated 3.5-4 hours for
465
intensive training and shaping of the more affected upper extremity with restraint of the less
466
affected one. The children were allowed 1-3 hours for their school work with the less affected
467
upper extremity. In addition, the mitten, rather than splinting or a univalved or bivalved cast,
468
was selected as a restraint to enhance the compliance as it is more convenient, lighter, and
469
easier to use.
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ACCEPTED MANUSCRIPT 471 472
Study Limitations Several study limitations should be considered. The inclusion criteria included mild to
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moderate impairment of upper limb function. Children with severely impaired upper limb
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function were not included. Thus, the study results cannot be generalized to all children with
476
CP. Using a uniform, familiar object (a ball) as the grasping target to assess treatment efficacy
477
may be another limitation. Using smaller objects than that used in this study may increase the
478
sensitivity for differentiating between possible changes after treatment. Despite these
479
limitations, this study demonstrates the beneficial effects of hCIT on motor control strategies
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and functional changes relative to those of TR.
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CONCLUSION
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hCIT induced better spatial and temporal control strategies underlying functional
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improvement than TR. hCIT generated smoother movement, more efficient hand grasping,
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and better movement preplanning and execution than TR. Furthermore, the beneficial effects
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on the motor control strategies, upper limb efficacy, and functional outcomes were maintained
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up to 6 months after the treatment.
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ACCEPTED MANUSCRIPT Figure Legends
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Figure 1. Flow diagram of the randomization procedure.
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Figure 2. The setup of the reach-to-grasp kinematic task (Trunk restraint is not shown).
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ACCEPTED MANUSCRIPT Table 1. Demographic and baseline characteristics of both groups
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Variables hCIT (n=23) TR (n=22) p value Age, years 8.73 (1.9) 8.66 (2.0) 0.909a Sex Boys 11 [48] 10 [46] 0.873b Girls 12 [52] 12 [54] More affected arm Right 12 [52] 11 [52] 0.884b Left 11 [48] 11 [48] BFMF Level I 3 [13] 3 [14] 0.953 b Level II 20 [87] 19 [86] Reach-to-grasp kinematics RT 0.57 (0.01) 0.57 (0.01) 0.954 a nMT 0.61 (0.05) 0.63 (0.03) 0.081 a nMU 0.29 (0.03) 0.27 (0.03) 0.037 a PV 65.11 (6.09) 65.16 (3.14) 0.953 a MGA 9.38 (0.95) 9.39 (0.88) 0.955 a PMGA 74.81 (18.93) 88.69 (13.24) 0.007 a PDMS-2 Grasping 39.65 (2.95) 38.73 (2.68) 0.277 a BOTMP Sub-8 4.91 (1.35) 4.64 (1.14) 0.461 a WeeFIM Self-care 39.57 (6.33) 37.41 (3.67) 0.169 a Values are expressed as mean (SD) or n [%]; a t tests; b chi-square tests. hCIT, home-based constraint-induced therapy; TR, traditional rehabilitation; BFMF, bimanual fine motor function; RT, reaction time; nMT, normalized movement time; nMU, normalized number of movement unit; PV, peak velocity; MGA, maximum grip aperture; PMGA, percent time where maximum grip aperture occurs; PDMS-2, Peabody Developmental Motor Scales-2; BOTMP, Bruininks-Oseretsky Test of Motor Proficiency; WeeFIM, Functional Independence Measure for Children.
ACCEPTED MANUSCRIPT
BOTMP Sub-8
hCIT (n=23)
TR (n=22)
43.96 (2.72)
41.27 (3.27)
8.87 (2.26)
7.86 (1.64)
hCIT (n=23)
TR (n=22)
61.15
