Kathleen Montpetit

Intravenous Bisphosphonate Therapy of Young Children with Osteogenesis Imperfecta: Skeletal Findings During Follow Up Throughout the Growing Years

Cyclical intravenous bisphosphonate therapy is widely used to treat children with osteogenesis imperfecta (OI), but little is known about long‐term treatment outcomes. We therefore reviewed 37 children with OI (OI type I, n = 1; OI type III, n = 14; and OI type IV, n = 22) who started intravenous bisphosphonate therapy before 5 years of age (median 2.2 years; range, 0.1 to 4.8 years), and who had a subsequent follow‐up period of at least 10 years (median 14.8 years; range, 10.7 to 18.2 years), during which they had received intravenous bisphosphonate treatment (pamidronate or zoledronic acid) for at least 6 years. During the observation period, the mean lumbar spine areal bone mineral density Z‐score increased from –6.6 (SD 3.1) to –3.0 (SD 1.8), and weight Z‐score increased from –2.3 (SD 1.5) to –1.7 (SD 1.7) (p < 0.001 and p = 0.008). At the time of the last assessment, patients with OI type IV had significantly higher height Z‐scores than a control group of patients matched for age, gender, and OI type who had not received bisphosphonates. Patients had a median of six femur fractures (range, 0 to 18) and five tibia fractures (range, 0 to 17) during the follow‐up period. At baseline, 35% of vertebra were affected by compression fractures, whereas only 6% of vertebra appeared compressed at the last evaluation (p < 0.001), indicating vertebral reshaping during growth. Spinal fusion surgery was performed in 16 patients (43%). Among the 21 patients who did not have spinal fusion surgery, 13 had scoliosis with a curvature ranging from 10 to 56 degrees. In conclusion, long‐term intravenous bisphosphonate therapy was associated with higher Z‐scores for lumbar spine areal bone mineral density and vertebral reshaping, but long‐bone fracture rates were still high and the majority of patients developed scoliosis.

Long-term functional benefits of selective dorsal rhizotomy for spastic cerebral palsy

OBJECT Large-scale natural history studies of gross motor development have shown that children with spastic cerebral palsy (CP) plateau during childhood and actually decline through adolescence. Selective dorsal rhizotomy (SDR) is a well-recognized treatment for spastic CP, but little is known about long-term outcomes of this treatment. The purpose of this study was to assess the durability of functional outcomes in a large number of patients through adolescence and into early adulthood using standardized assessment tools. METHODS The authors analyzed long-term follow-up data in children who had been evaluated by a multidisciplinary team preoperatively and at 1, 5, 10, and 15 years after SDR. These evaluations included quantitative, standardized assessments of lower-limb tone (Ashworth Scale), Gross Motor Function Measure (GMFM), and performance of activities of daily living (ADLs) by the Pediatric Evaluation of Disability Inventory in children who had been stratified by motor severity using the Gross Motor Function Classification System (GMFCS). In addition, group-based trajectory modeling (GBTM) was used to identify any heterogeneity of response to SDR among these treated children, and to find which pretreatment variables might be associated with this heterogeneity. Finally, a chart review of adjunct orthopedic procedures required by these children following SDR was performed. RESULTS Of 102 patients who underwent preoperative evaluations, 97, 62, 57, and 14 patients completed postoperative assessments at 1, 5, 10, and 15 years, respectively. After SDR, through adolescence and into early adulthood, statistically significant durable improvements in lower-limb muscle tone, gross motor function, and performance of ADLs were found. When stratified by the GMFCS, long-lasting improvements for GMFCS Groups I, II, and III were found. The GBTM revealed 4 groups of patients who responded differently to SDR. This group assignment was associated with distribution of spasticity (diplegia was associated with better outcomes than triplegia or quadriplegia) and degree of hip adductor spasticity (Ashworth score < 3 was associated with better outcomes than a score of 3), but not with age, sex, degree of ankle plantar flexion spasticity, or degree of hamstring spasticity. In a sample of 88 patients who had complete records of orthopedic procedures and botulinum toxin (Botox) injections, 52 (59.1%) underwent SDR alone, 11 (12.5%) received only Botox injections in addition to SDR, while 25 patients (28.4%) needed further lower-extremity orthopedic surgery after SDR. CONCLUSIONS In the majority of patients, the benefits of SDR are durable through adolescence and into early adulthood. These benefits include improved muscle tone, gross motor function, and performance of ADLs, as well as a decreased need for adjunct orthopedic procedures or Botox injections. The children most likely to display these long-term benefits are those in GMFCS Groups I, II, and III, with spastic diplegia, less hip adductor spasticity, and preoperative GMFM scores greater than 60.

Evaluation of an Item Bank for a Computerized Adaptive Test of Activity in Children With Cerebral Palsy

Background: Contemporary clinical assessments of activity are needed across the age span for children with cerebral palsy (CP). Computerized adaptive testing (CAT) has the potential to efficiently administer items for children across wide age spans and functional levels. Objective: The objective of this study was to examine the psychometric properties of a new item bank and simulated computerized adaptive test to assess activity level abilities in children with CP. Design: This was a cross-sectional item calibration study. Methods: The convenience sample consisted of 308 children and youth with CP, aged 2 to 20 years (X=10.7, SD=4.0), recruited from 4 pediatric hospitals. We collected parent-report data on an initial set of 45 activity items. Using an Item Response Theory (IRT) approach, we compared estimated scores from the activity item bank with concurrent instruments, examined discriminate validity, and developed computer simulations of a CAT algorithm with multiple stop rules to evaluate scale coverage, score agreement with CAT algorithms, and discriminant and concurrent validity. Results: Confirmatory factor analysis supported scale unidimensionality, local item dependence, and invariance. Scores from the computer simulations of the prototype CATs with varying stop rules were consistent with scores from the full item bank (r=.93–.98). The activity summary scores discriminated across levels of upper-extremity and gross motor severity and were correlated with the Pediatric Outcomes Data Collection Instrument (PODCI) physical function and sports subscale (r=.86), the Functional Independence Measure for Children (Wee-FIM) (r=.79), and the Pediatric Quality of Life Inventory–Cerebral Palsy version (r=.74). Limitations: The sample size was small for such IRT item banks and CAT development studies. Another limitation was oversampling of children with CP at higher functioning levels. Conclusions: The new activity item bank appears to have promise for use in a CAT application for the assessment of activity abilities in children with CP across a wide age range and different levels of motor severity.

Measuring global physical health in children with cerebral palsy: illustration of a multidimensional bi-factor model and computerized adaptive testing

PurposeThe purposes of this study were to apply a bi-factor model for the determination of test dimensionality and a multidimensional CAT using computer simulations of real data for the assessment of a new global physical health measure for children with cerebral palsy (CP).MethodsParent respondents of 306 children with cerebral palsy were recruited from four pediatric rehabilitation hospitals and outpatient clinics. We compared confirmatory factor analysis results across four models: (1) one-factor unidimensional; (2) two-factor multidimensional (MIRT); (3) bi-factor MIRT with fixed slopes; and (4) bi-factor MIRT with varied slopes. We tested whether the general and content (fatigue and pain) person score estimates could discriminate across severity and types of CP, and whether score estimates from a simulated CAT were similar to estimates based on the total item bank, and whether they correlated as expected with external measures.ResultsConfirmatory factor analysis suggested separate pain and fatigue sub-factors; all 37 items were retained in the analyses. From the bi-factor MIRT model with fixed slopes, the full item bank scores discriminated across levels of severity and types of CP, and compared favorably to external instruments. CAT scores based on 10- and 15-item versions accurately captured the global physical health scores.ConclusionsThe bi-factor MIRT CAT application, especially the 10- and 15-item versions, yielded accurate global physical health scores that discriminated across known severity groups and types of CP, and correlated as expected with concurrent measures. The CATs have potential for collecting complex data on the physical health of children with CP in an efficient manner.

Activities and participation in young adults with osteogenesis imperfecta.

The objective of this cross-sectional study was to compare the activities and participation in the domains of mobility, self-care, domestic life and social functioning in young adults according to osteogenesis imperfecta (OI) type. Fifty-four former OI patients were invited to participate and were sent a structured questionnaire. Twenty-four patients (mean age: 25.0 years, SD: 2.6 years) with OI types I (n=7), III (n=7), IV (n =8) and V (n=2) completed the questionnaire. Participants with OI type I reported full independence, and only few respondents with OI types IV and V reported some limitations in mobility and domestic life activities. Young adults with OI type III had significantly lower activity scores in aspects of mobility and domestic life and lower levels of participation in employment, sporting activities and transportation. Participation in leisure and social interactions were not different across OI types. Young adults with more severe types of osteogenesis imperfecta have greater activity limitations and participation restrictions. Our findings indicate the importance of promoting and facilitating involvement in meaningful activities and roles in young adults with moderate to severe forms of OI.

Validity and Reliability of Physical Functioning Computer-adaptive Tests for Children With Cerebral Palsy

Background The purpose of this study was to assess the concurrent validity and reliability of scores from 4 new parent-report computer-adapted testing (CAT) programs developed to measure the physical functioning of children with cerebral palsy (CP). The Shriners Hospitals for Children CP-CAT battery includes upper-extremity skills, lower-extremity and mobility skills, activity, and global physical health. Methods This was a prospective study of 91 children with CP who were tested cross-sectionally and 27 children with CP who were administered the CP-CAT programs twice within approximately a 1-month interval. We examined the concurrent validity of the 4 Shriners Hospitals for Children CP-CAT programs by Pearson correlations with comparative parent-report instruments. The scale reliability was tested by developing estimates of marginal reliability; test-retest reliability was assessed by intraclass correlations. Results Pearson correlations were moderate to high in matching content domains of the CATs with the comparison measures. Marginal reliability estimates were always better for the CAT program than the comparative instruments. Average test-retest reliability using Intraclass correlations across the 4 CATs was ICC3,1=0.91 with a range of 0.88 to 0.94. Conclusions We found the CAT scores to be related to expected domains from external instruments, to have good scale reliability, and to have stable scores as determined by test-retest reliability. These results support the use of parent-report CATs in the assessment of physical functioning in children with CP. Level of Evidence This is a level 2 prospective study designed to establish the validity and reliability of CAT as an evaluation method.

Development of a parent-report computer-adaptive test to assess physical functioning in children with cerebral palsy II: upper-extremity skills

The specific aims of this study were to (1) examine the psychometric properties (unidimensionality, differential item functioning, scale coverage) of an item bank of upper‐extremity skills for children and adolescents with cerebral palsy (CP); (2) evaluate a simulated computer‐adaptive test (CAT) using this item bank; (3) examine the concurrent validity of the CAT with the Pediatric Outcomes Data Collection Instrument (PODCI) upper‐extremity core scale; and (4) determine the discriminant validity of the simulated CAT with Manual Ability Classification System (MACS) levels and CP type (i.e. diplegia, hemiplegia, or quadriplegia). Parents (n=180) of children and adolescents with CP (spastic diplegia 49%, hemiplegia 22%, or quadriplegia 28%) consisting of 102 males and 78 females with a mean age of 10 years 6 months (SD 4y 1mo, range 2–21y), and MACS levels I through V participated in calibration of an item pool and completed the PODCI. Confirmatory factor analyses supported a unidimensional model using 49 of the 53 upper‐extremity items. Simulated CATs of 5, 10, and 15 items demonstrated excellent accuracy (intraclass correlation coefficient [ICCs] >0.93) with the full item bank, had high correlations with the PODCI upper‐extremity core scale score (ICC 0.79), and discriminated among MACS levels. The simulated CATs demonstrated excellent overall content coverage over a wide age span and severity of upper‐extremity involvement. The future development and refinement of CATs for parent report of physical function in children and adolescents with CP is supported by our work.

Multidisciplinary Treatment of Severe Osteogenesis Imperfecta: Functional Outcomes at Skeletal Maturity

OBJECTIVE To determine the functional outcomes associated with long-term multidisciplinary treatment, intravenous bisphosphonate treatment, orthopedic surgery, and rehabilitation in children with severe osteogenesis imperfecta (OI) (diagnosed clinically as OI types III or IV). DESIGN Retrospective study where outcomes were measured prospectively. SETTING Pediatric orthopedic hospital. PARTICIPANTS Adolescents (N=41; age range, 15-21y) with severe OI (OI type III: n=17; OI type IV: n=24) who had started therapy before the age of 6 years, had received treatment for at least 10 years, and had achieved final height. INTERVENTIONS Intravenous bisphosphonate treatment, orthopedic surgery, and rehabilitation. MAIN OUTCOME MEASURE Pediatric Evaluation of Disability Inventory. RESULTS At the time of the last available follow-up examination, none of the individuals diagnosed with OI type III (most severely affected group) was able to ambulate without ambulation aids, whereas 20 (83%) patients with OI type IV were able to ambulate without ambulation aids. Regarding self-care, we specifically assessed 8 skills that we deemed essential for living independently (grooming; dressing; toileting; bed, chair, toilet, tub, and car transfers). Only 6 (35%) of the youths with OI type III were able to complete all 8 items, whereas 23 (96%) individuals with OI type IV managed to perform all tasks. Teens with OI type III often needed assistance for the transfer to toilet, tub, and car and for personal hygiene and clothing management associated with toileting, usually because of limitations in upper-extremity function. CONCLUSIONS These observations suggest that further improvements in the functional status of the most severely affected children with OI are contingent on advances in the clinical management of upper-extremity issues.

A prospective evaluation of the WeeFIM in patients with cerebral palsy undergoing orthopaedic surgery.

Purpose: Although frequently used in pediatric rehabilitation settings, the WeeFIM has not been tested in surgical pediatric orthopaedic patients. Methods: The WeeFIM was administered to patients with surgical cerebral palsy at defined intervals preoperatively and at both 6 and 12 months postoperatively. The age-adjusted change scores from baseline to follow-up were tested both parametrically and nonparametrically. Results: Four hundred sixty-eight patients had baseline evaluations. There were 161 six-month follow-up assessments and 108 twelve-month follow-up assessments. The baseline WeeFIM was able to separate children with different patterns of cerebral palsy. Hemiplegic patients had higher scores than diplegic and tetraplegic patients. Overall age-adjusted scores were improved at both 6 (mean increase 2.0) and 12 months (mean increase 2.2). The instrument showed significant ceiling effects for diplegic and hemiplegic patients with lower or upper extremity surgery and limited responsiveness for lower extremity surgery in tetraplegic patients. Parametrically, it showed improvements in mobility for both rhizotomy and tetraplegic upper extremity surgery. Nonparametric tests were not significant for rhizotomy mobility improvement. Conclusions: Although the WeeFIM adequately reflects the severity of neurological involvement in pediatric orthopaedic patients with cerebral palsy, it has a significant ceiling effect in diplegic and hemiplegic patients limiting responsiveness and lacks content validity for tetraplegic patients. The instrument may have some use in tetraplegic patients with upper extremity surgery and in rhizotomy patients. We recommend against its general use for orthopaedic surgery in patients with cerebral palsy lower extremity or spine surgery and in hemiplegic patients with upper extremity surgery.

Using cognitive interviewing for test items to assess physical function in children with cerebral palsy.

Purpose: The purpose of this study was to assess the content, format, and comprehension of test items and responses developed for use in a computer adaptive test (CAT) of physical function for children with cerebral palsy (CP). Methods: After training in cognitive interviewing techniques, investigators defined item intent and developed questions for each item. Parents of children with CP (n = 27) participated in interviews probing item meaning, item wording, and response choice adequacy and appropriateness. Results: Qualitative analysis identified 3 themes: item clarity; relevance, context, and attribution; and problems with wording or tone. Parents reported the importance of delineating task components, assistance amount, and environmental context. Conclusion: Cognitive interviewing provided valuable information about the validity of new items and insight to improve relevance and context. We believe that the development of CATs in pediatric rehabilitation may ultimately reduce the impact of the issues identified.