Long-term survival outcomes of patients with Niemann-Pick disease type C receiving miglustat treatment: A large retrospective observational study.

Miglustat has been indicated for the treatment of Niemann-Pick disease type C (NP-C) since 2009. The aim of this observational study was to assess the effect of miglustat on long-term survival of patients with NP-C. Data for 789 patients from five large national cohorts and from the NPC Registry were collected and combined. Miglustat-treated and untreated patients overall and within sub-groups according to age-at-neurological-onset, that is, early infantile-onset (<2 years), late infantile-onset (2 to <6 years), juvenile-onset (6 to <15 years), and adolescent/adult-onset (≥15 years) were analysed and compared. Survival was analysed from the time of first neurological manifestation (Neurological onset group, comprising 669 patients) and from diagnosis (Diagnosis group, comprising 590 patients) using a Cox proportional hazard model adjusted for various covariates. Overall, 384 (57.4%) patients in the Neurological onset group and 329 (55.8%) in the Diagnosis group were treated with miglustat. Miglustat treatment was associated with a significant reduction in risk of mortality in both groups (entire Neurological onset group, Hazard ratio [HR] = 0.51; entire Diagnosis group, HR = 0.44; both P < .001). The effect was observed consistently in all age-at-neurological-onset sub-groups (HRs = 0.3 to 0.7) and was statistically significant for late infantile-onset patients in both groups (Neurological onset group, HR = 0.36, P < .05; Diagnosis group, HR = 0.32, P < .01), and juvenile-onset patients in the Diagnosis group only (HR = 0.30, P < .05). Despite the limitations of the data that urge cautious interpretation, the findings are consistent with a beneficial effect of miglustat on survival in patients with NP-C.

The Niemann-Pick C1 gene interacts with a high-fat diet to promote weight gain through differential regulation of central energy metabolism pathways.

A genome-wide association study (GWAS) reported that common variation in the human Niemann-Pick C1 gene (NPC1) is associated with morbid adult obesity. This study was confirmed using our BALB/cJ Npc1 mouse model, whereby heterozygous mice (Npc1+/- ) with decreased gene dosage were susceptible to weight gain when fed a high-fat diet (HFD) compared with homozygous normal mice (Npc1+/+ ) fed the same diet. The objective for our current study was to validate this Npc1 gene-diet interaction using statistical modeling with fitted growth trajectories, conduct body weight analyses for different measures, and define the physiological basis responsible for weight gain. Metabolic phenotype analysis indicated no significant difference between Npc1+/+ and Npc1+/- mice fed a HFD for food and water intake, oxygen consumption, carbon dioxide production, locomotor activity, adaptive thermogenesis, and intestinal lipid absorption. However, the livers from Npc1+/- mice had significantly increased amounts of mature sterol regulatory element-binding protein-1 (SREBP-1) and increased expression of SREBP-1 target genes that regulate glycolysis and lipogenesis with an accumulation of triacylglycerol and cholesterol. Moreover, white adipose tissue from Npc1+/- mice had significantly decreased amounts of phosphorylated hormone-sensitive lipase with decreased triacylglycerol lipolysis. Consistent with these results, cellular energy metabolism studies indicated that Npc1+/- fibroblasts had significantly increased glycolysis and lipogenesis, in addition to significantly decreased substrate (glucose and endogenous fatty acid) oxidative metabolism with an accumulation of triacylglycerol and cholesterol. In conclusion, these studies demonstrate that the Npc1 gene interacts with a HFD to promote weight gain through differential regulation of central energy metabolism pathways.

DSM Criteria that Best Differentiate Intellectual Disability from Autism Spectrum Disorder.

Clinical characteristics of autism spectrum disorder (ASD) and intellectual disability (ID) overlap, creating potential for diagnostic confusion. Diagnostic and statistical manual of mental disorders (DSM) criteria that best differentiate children with ID and some ASD features from those with comorbid ID and ASD were identified. Records-based surveillance of ASD among 8-year-old children across 14 US populations ascertained 2816 children with ID, with or without ASD. Area under the curve (AUC) was conducted to determine discriminatory power of DSM criteria. AUC analyses indicated that restricted interests or repetitive behaviors best differentiated between the two groups. A subset of 6 criteria focused on social interactions and stereotyped behaviors was most effective at differentiating the two groups (AUC of 0.923), while communication-related criteria were least discriminatory. Matching children with appropriate treatments requires differentiation between ID and ASD. Shifting to DSM-5 may improve differentiation with decreased emphasis on language-related behaviors.

Health services received by individuals with duchenne/becker muscular dystrophy.

INTRODUCTION: Anecdotal reports from families and care providers suggest a wide variation in services received by individuals with Duchenne/Becker muscular dystrophy (DBMD). METHODS: We documented the type and frequency of health services received by individuals with DBMD using the Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet) interview data released in June 2012. Interviews with eligible caregivers from 5 sites (Arizona, Colorado, Georgia, Iowa, and western New York) were conducted from April 2007 to March 2012. RESULTS: Two hundred ninety-six caregivers (66% of those contactable) participated in the interview. There were significant differences among sites in the specialists seen and services received. Concurrence with cardiac recommendations was higher than that with respiratory recommendations. CONCLUSIONS: The results of this survey support and quantify the anecdotal reports from families and care providers regarding the disparities in services received by individuals with DBMD. It remains to be determined whether these differences affect outcomes.

Fetal alcohol syndrome among children aged 7-9 years - Arizona, Colorado, and New York, 2010.

Fetal alcohol syndrome (FAS) is a serious birth defect and developmental disorder caused by in utero exposure to alcohol. Assessment of the public health burden of FAS through surveillance has proven difficult; there is wide variation in reported prevalence depending on the study population and surveillance method. Generally, records-based birth prevalence studies report estimates of 0.2-1.5 per 1,000 live births, whereas studies that use in-person, expert assessment of school-aged children in a community report estimates of 6-9 per 1,000 population. The Fetal Alcohol Syndrome Surveillance Network II addressed some of the challenges in records-based ascertainment by assessing a period prevalence of FAS among children aged 7‒9 years in Arizona, Colorado, and New York. The prevalence across sites ranged from 0.3 to 0.8 per 1,000 children. Prevalence of FAS was highest among American Indian/Alaska Native children and lowest among Hispanic children. These estimates continue to be much lower than those obtained from studies using in-person, expert assessment. Factors that might contribute to this discrepancy include 1) inadequate recognition of the physical and behavioral characteristics of FAS by clinical care providers; 2) insufficient documentation of those characteristics in the medical record; and 3) failure to consider prenatal alcohol exposure with diagnoses of behavioral and learning problems. Addressing these factors through training of medical and allied health providers can lead to practice changes, ultimately increasing recognition and documentation of the characteristics of FAS.

Methods for surveillance of fetal alcohol syndrome: The Fetal Alcohol Syndrome Surveillance Network II (FASSNetII) - Arizona, Colorado, New York, 2009 - 2014.

Surveillance of fetal alcohol syndrome (FAS) is important for monitoring the effects of prenatal alcohol exposure and describing the public health burden of this preventable disorder. Building on the infrastructure of the Fetal Alcohol Syndrome Surveillance Network (FASSNet, 1997-2002), in 2009 the Centers for Disease Control and Prevention awarded 5-year cooperative agreements to three states, Arizona, Colorado, and New York, to conduct population-based surveillance of FAS. The Fetal Alcohol Syndrome Surveillance Network II (FASSNetII, 2009-2014) developed a surveillance case definition based on three clinical criteria: characteristic facial features, central nervous system abnormalities, and growth deficiency. FASSNetII modified the FASSNet methods in three important ways: (1) estimation of a period prevalence rather than birth prevalence; (2) surveillance of FAS among school-age children (ages 7-9 years) to better document the central nervous system abnormalities that are not apparent at birth or during infancy; and (3) implementation of an expert clinical review of abstracted data for probable and confirmed cases classified through a computerized algorithm. FASSNetII abstracted data from multiple sources including birth records, medical records from child development centers or other specialty clinics, and administrative databases such as hospital discharge and Medicaid. One challenge of FASSNetII was its limited access to non-medical records. The FAS prevalence that could be estimated was that of the population identified through an encounter with the healthcare system. Clinical and public health programs that identify children affected by FAS provide critical information for targeting preventive, medical and educational services in this vulnerable population.

Diagnostic and clinical characteristics of early-manifesting females with Duchenne or Becker muscular dystrophy.

Manifestations of Duchenne and Becker muscular dystrophy (DBMD) are present in up to 40% of heterozygous females, but there are few reports of females who exhibit skeletal muscle symptoms in childhood. From the Muscular Dystrophy Surveillance Tracking and Research Network, a multi-site population-based surveillance network for dystrophinopathy, nine symptomatic female heterozygotes with onset of symptoms prior to age 9 years were identified. The median age at diagnosis was 8.3 years, and the median interval from first symptoms to diagnosis was 1.35 years. Of the nine female heterozygotes, four had a positive family history, seven had intellectual disability and five had at least one mental health disorder. Mental health concerns included attention deficit hyperactivity disorder (ADHD), autism spectrum features, bipolar disorder, and depression. The frequency of intellectual and mental health problems in this group is higher than previously reported for affected males and for symptomatic females. These findings may have implications for diagnosis of early manifesting heterozygotes and for their health supervision.

Correlates of care for young men with Duchenne and Becker muscular dystrophy.

INTRODUCTION: In progressive conditions, such as Duchenne and Becker muscular dystrophy (DBMD), the need for care may outpace care use. We examined correlates that contribute to utilization of needed care. METHODS: Structured interviews were conducted on use of care among 34 young men with DBMD who were born before 1982. RESULTS: Disease severity, per capita income, and presence of other relatives with DBMD predicted greater use of services. Race/ethnicity, acculturation, and level of caregiver education did not significantly predict service utilization. CONCLUSIONS: We identified disparities in receipt of healthcare and related services in adult men with DBMD that can affect quality of life. Despite the high disease severity identified in this population, these men utilized only half of the services available to individuals with significant progressive conditions. Providers should be aware of low service utilization and focus on awareness and assistance to ensure access to available care.

Sibling concordance for clinical features of Duchenne and Becker muscular dystrophies.

INTRODUCTION: The correlation of markers of disease severity among brothers with Duchenne or Becker muscular dystrophy has implications for clinical guidance and clinical trials. METHODS: Sibling pairs with Duchenne or Becker muscular dystrophy (n = 60) were compared for ages when they reached clinical milestones of disease progression, including ceased ambulation, scoliosis of ≥ 20°, and development of cardiomyopathy. RESULTS: The median age at which younger brothers reached each milestone, compared with their older brothers ranged from 25 months younger for development of cardiomyopathy to 2 months older for ceased ambulation. For each additional month of ambulation by the older brother, the hazard of ceased ambulation by the younger brother decreased by 4%. CONCLUSIONS: The ages when siblings reach clinical milestones of disease vary widely between siblings. However, the time to ceased ambulation for older brothers predicts the time to ceased ambulation for their younger brothers.

Exploring the feasibility of using electronic health records in the surveillance of fetal alcohol syndrome.

BACKGROUND: Explore the use of electronic health records (EHRs) in fetal alcohol syndrome (FAS) surveillance systems. METHODS: Using EHRs we identified diagnoses and anthropometric measurements related to the FAS criteria developed by the Fetal Alcohol Syndrome Surveillance Network (FASSNet) among children aged 0 to 12 years. RESULTS: There were 143,393 distinct children aged between 0 and 12 years enrolled in Kaiser Permanente, Georgia, during the study period. Based on diagnoses and anthropometric measurements, 20,101 children met at least one criterion of interest, and when grouped into combinations of different criteria there were 2285 who met GROWTH+CNS criteria, 76 children who met GROWTH+FACE criteria, 107 children who met CNS+FACE criteria, and 93 children who met GROWTH+CNS+FACE criteria. The prevalence of FAS as defined by FASSNet is 1.92 per 1000 children. We linked 17,084 (85.0%) children to their mothers in the health plan; only 3% of mothers of children in the GROWTH+CNS+FACE group had an indication of alcohol or drugs use, but they had the highest rate of depression (39%). CONCLUSION: Data of utility in identification of FAS are readily available in EHRs and may serve as a basis for intervention with at-risk children and in planning of future FAS surveillance programs.

Patterns of growth in ambulatory males with Duchenne muscular dystrophy.

OBJECTIVE: To provide weight-for-age, height-for-age, and body mass index-for-age growth reference standards for ambulatory, steroid-naïve males, ages 2-12 years, with Duchenne muscular dystrophy (DMD) and to compare these growth curves to the 2000 Centers for Disease Control and Prevention growth charts for boys, which serve as references of physical size and growth for the general male pediatric population in the US. STUDY DESIGN: Through a multi-state population-based surveillance of individuals with muscular dystrophy, a total of 1877 weight and 1544 height measurements ascertained during 1985-2010 from 513 males with DMD were obtained retrospectively from medical record review. Cases were classified as DMD if loss of ambulation occurred before the 12th birthday or, if younger than 12 years and still ambulating, the earliest symptoms of dystrophinopathy occurred before the 6th birthday. Each growth chart was constructed using 5 percentiles: 10th, 25th, 50th, 75th, and 90th. Smoothing procedures were applied in 2 stages to the irregular plots of the empirical percentile values. RESULTS: A set of growth curves, derived from a large cohort of male youth with DMD, are presented. These curves demonstrate that DMD males are shorter and tend to the extremes of weight and body mass index compared with the general male pediatric population in the US. CONCLUSION: Charts representing the pattern of growth in ambulatory, steroid-naïve males with DMD can facilitate monitoring of growth and early detection of unusual growth patterns. Use of these growth standards also will assist in monitoring responses to corticosteroid treatment.

Oral corticosteroids and onset of cardiomyopathy in Duchenne muscular dystrophy.

OBJECTIVE: To estimate the age when cardiomyopathy develops in boys with Duchenne muscular dystrophy (DMD) and to analyze the effect of corticosteroid treatment on the age of cardiomyopathy onset. STUDY DESIGN: We identified a population-based sample of 462 boys with DMD, born between 1982 and 2005, in 5 surveillance sites in the US. Echocardiographic and corticosteroid treatment data were collected. Cardiomyopathy was defined by a reduced fractional shortening (<28%) or ejection fraction (<55%). The age of cardiomyopathy onset was determined. Survival analysis was performed to determine the effects of corticosteroid treatment on cardiomyopathy onset. RESULTS: The mean (SD) age of cardiomyopathy onset was 14.3 (4.2) years for the entire population and 15.2 (3.4) years in corticosteroid-treated vs 13.1 (4.8) in non-treated boys. Survival analysis described a significant delay of cardiomyopathy onset for boys treated with corticosteroids (P < .02). By 14.3 years of age, 63% of non-treated boys had developed cardiomyopathy vs only 36% of those treated. Among boys treated with corticosteroids, there is a significant positive effect of duration of corticosteroid treatment on cardiomyopathy onset (P < .0001). For every year of corticosteroid treatment, the probability of developing cardiomyopathy decreased by 4%. CONCLUSIONS: Oral corticosteroid treatment was associated with delayed cardiomyopathy onset. The duration of corticosteroid treatment also correlated positively with delayed cardiomyopathy onset. Our analysis suggests that a boy with DMD treated for 5 years with corticosteroids might experience a 20% decrease in the likelihood of developing cardiomyopathy compared with untreated boys.

Remote diagnosis of congenital heart disease in southern Arizona: comparison between tele-echocardiography and videotapes.

OBJECTIVE: We report our experience with tele-echocardiography and echocardiograms recorded digitally or on videotape (recorded-echos) at The University of Arizona from August 2006 to December 2010 and compare their quality and diagnostic accuracy. MATERIALS AND METHODS: Tele-echocardiograms (tele-echos) were transmitted from the Yuma Regional Medical Center to The University of Arizona via a T-1 and aT-3 line at a bandwidth of 768 kilobits per second. Recorded-echos were shipped for interpretation to The University of Arizona by overnight mail. Diagnostic accuracy was assessed by comparing tele- and recorded-echos with electrocardiograms performed by a pediatric cardiologist (PedsCard-echos). RESULTS: Three hundred forty-six tele-echos in 260 patients and 455 recorded-echos in 406 patients were performed (median age, 6 and 8 days, respectively). Indications included possible congenital heart disease (CHD), patent ductus arteriosus (PDA), and persistent pulmonary hypertension of the newborn. Diagnostic categories included complex CHD, non-critical disease, PDA, and other. PedsCard-echos were available for 27% of the tele-echo and 30% of the recorded-echo patients. Comparisons between tele- and PedsCard-echo yielded no discrepancies in 12 (23%), expected resolution of condition in 26 (49%), and minor in 14 (26%). One (2%) major discrepancy was detected. Comparisons between recorded- and PedsCard-echo showed no discrepancies in 28 (40%), expected resolution of condition in 14 (20%), and minor discrepancies in 28 (40%) patients. No significant difference with respect to discrepancies was detected between tele- and recorded-echos. There was significant (p<0.01) improvement in tele- and recorded-echo study quality by 2010. CONCLUSIONS: (1) Tele-echocardiography can be performed successfully with excellent accuracy. (2) The quality of tele- and recorded-echo studies improved toward the end of the analysis period. (3) Although initially tele-echo studies were more accurate than recorded-echo studies, there was no difference between these two types of studies by the fourth year of the study. (4) Both tele- and recorded-echos were indispensible in the remote diagnosis of CHD.

Disparities in the diagnostic process of Duchenne and Becker muscular dystrophy.

PURPOSE: To determine whether sociodemographic factors are associated with delays at specific steps in the diagnostic process of Duchenne and Becker muscular dystrophy. METHODS: We examined abstracted medical records for 540 males from population-based surveillance sites in Arizona, Colorado, Georgia, Iowa, and western New York. We used linear regressions to model the association of three sociodemographic characteristics with age at initial medical evaluation, first creatine kinase measurement, and earliest DNA analysis while controlling for changes in the diagnostic process over time. The analytical dataset included 375 males with information on family history of Duchenne and Becker muscular dystrophy, neighborhood poverty levels, and race/ethnicity. RESULTS: Black and Hispanic race/ethnicity predicted older ages at initial evaluation, creatine kinase measurement, and DNA testing (P < 0.05). A positive family history of Duchenne and Becker muscular dystrophy predicted younger ages at initial evaluation, creatine kinase measurement and DNA testing (P < 0.001). Higher neighborhood poverty was associated with earlier ages of evaluation (P < 0.05). CONCLUSIONS: Racial and ethnic disparities in the diagnostic process for Duchenne and Becker muscular dystrophy are evident even after adjustment for family history of Duchenne and Becker muscular dystrophy and changes in the diagnostic process over time. Black and Hispanic children are initially evaluated at older ages than white children, and the gap widens at later steps in the diagnostic process.

Palliative care services in families of males with Duchenne muscular dystrophy.

INTRODUCTION: Palliative care services that address physical pain and emotional, psychosocial, and spiritual needs may benefit individuals with Duchenne muscular dystrophy (DMD). METHODS: The objective of this study was to describe the palliative care services that families of males with DMD report they receive. A questionnaire was administered to families of males with DMD born prior to January 1, 1982. Thirty-four families responded. RESULTS: Most families (85%) had never heard the term palliative care. Only attendant care and skilled nursing services showed much usage, with 44% and 50% indicating receipt of these services, respectively. Receipt of other services was reported less frequently: pastoral care (27%); respite care (18%); pain management (12%); and hospice care (6%). Only 8 respondents (25%) reported having any type of directive document in place. CONCLUSION: The data suggest a need for improved awareness of palliative care and related services among families of young men with DMD.

The National Niemann-Pick Type C1 Disease Database: correlation of lipid profiles, mutations, and biochemical phenotypes.

Niemann-Pick type C1 disease (NPC1) is an autosomal recessive lysosomal storage disorder characterized by neonatal jaundice, hepatosplenomegaly, and progressive neurodegeneration. The present study provides the lipid profiles, mutations, and corresponding associations with the biochemical phenotype obtained from NPC1 patients who participated in the National NPC1 Disease Database. Lipid profiles were obtained from 34 patients (39%) in the survey and demonstrated significantly reduced plasma LDL cholesterol (LDL-C) and increased plasma triglycerides in the majority of patients. Reduced plasma HDL cholesterol (HDL-C) was the most consistent lipoprotein abnormality found in male and female NPC1 patients across age groups and occurred independent of changes in plasma triglycerides. A subset of 19 patients for whom the biochemical severity of known NPC1 mutations could be correlated with their lipid profile showed a strong inverse correlation between plasma HDL-C and severity of the biochemical phenotype. Gene mutations were available for 52 patients (59%) in the survey, including 52 different mutations and five novel mutations (Y628C, P887L, I923V, A1151T, and 3741_3744delACTC). Together, these findings provide novel information regarding the plasma lipoprotein changes and mutations in NPC1 disease, and suggest plasma HDL-C represents a potential biomarker of NPC1 disease severity.

Palliative care services in families of males with muscular dystrophy: Data from MD STARnet.

INTRODUCTION: Information on use of palliative care services among individuals with Duchenne and Becker muscular dystrophy is scant despite the clearly documented need. METHODS: We examined associations between uptake of palliative care services by 233 males with Duchenne and Becker muscular dystrophy aged 12 and older for both caregiver and affected male characteristics using the Muscular Dystrophy Surveillance Tracking and Research Network baseline interview. RESULTS: Ninety-one percent of caregivers (213/233) used at least one palliative care service. Case management had the highest frequency of use (59%). Use of palliative care was more frequently associated with the characteristics of affected males, as were some individual palliative care services. Utilization of six individual services differed among Muscular Dystrophy Surveillance Tracking and Research Network sites. While research suggests that pain is a frequent problem in Duchenne and Becker muscular dystrophy, only 12.5% reported use of pain management services. DISCUSSION: Although palliative care use among families of males with Duchenne and Becker muscular dystrophy is high overall, there is much variability in use of individual services. Use of palliative care is driven by disease experience in the affected male. Many of the care recommendations for these individuals highlight the importance for early involvement of palliative care professionals.

Recognition of clinical characteristics for population-based surveillance of fetal alcohol syndrome.

BACKGROUND: The diagnosis of fetal alcohol syndrome (FAS) rests on identification of characteristic facial, growth, and central nervous system (CNS) features. Public health surveillance of FAS depends on documentation of these characteristics. We evaluated if reporting of FAS characteristics is associated with the type of provider examining the child. METHODS: We analyzed cases aged 7-9 years from the Fetal Alcohol Syndrome Surveillance Network II (FASSNetII). We included cases whose surveillance records included the type of provider (qualifying provider: developmental pediatrician, geneticist, neonatologist; other physician; or other provider) who evaluated the child as well as the FAS diagnostic characteristics (facial dysmorphology, CNS impairment, and/or growth deficiency) reported by the provider. RESULTS: A total of 345 cases were eligible for this analysis. Of these, 188 (54.5%) had adequate information on type of provider. Qualifying physicians averaged more than six reported FAS characteristics while other providers averaged less than five. Qualifying physicians reported on facial characteristics and developmental delay more frequently than other providers. Also, qualifying physicians reported on all three domains of characteristics (facial, CNS, and growth) in 97% of cases while others reported all three characteristics on two thirds of cases. CONCLUSIONS: Documentation in medical records during clinical evaluations for FAS is lower than optimal for cross-provider communication and surveillance purposes. Lack of documentation limits the quality and quantity of information in records that serve as a major source of data for public health surveillance systems.

Implementation of Duchenne Muscular Dystrophy Care Considerations.

BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked disorder characterized by progressive muscle weakness and multisystem involvement. Recent advances in management of individuals with DMD have prolonged survival. Lack of standardized care spurred an international collaboration to develop consensus-based care considerations for diagnosis and management. In this study, we evaluate adherence to considerations at selected sites. METHODS: We collaborated with the Muscular Dystrophy Surveillance, Tracking, and Research Network. Our sample included males with DMD and Becker muscular dystrophy <21 years as of December 31, 2010, with 1 health care encounter on or after January 1, 2012. We collected data from medical records on encounters occurring January 1, 2012, through December 31, 2014. Adherence was determined when frequency of visits or assessments were at or above recommendations for selected care considerations. RESULTS: Our analytic sample included 299 individuals, 7% of whom (20/299) were classified as childhood-onset Becker muscular dystrophy. Adherence for neuromuscular and respiratory clinician visits was 65% for the cohort; neuromuscular assessments and corticosteroid side effect monitoring measures ranged from 16% to 68%. Adherence was 83% for forced vital capacity and ≤58% for other respiratory diagnostics. Cardiologist assessments and echocardiograms were found for at least 84%. Transition planning for education or health care was documented for 31% of eligible males. CONCLUSIONS: Medical records data were used to identify areas in which practice aligns with the care considerations. However, there remains inconsistency across domains and insufficiency in critical areas. More research is needed to explain this variability and identify reliable methods to measure outcomes.

Confirmatory factor analysis in osteopathic medicine: fascial and spinal motion restrictions as correlates of muscle spasticity in children with cerebral palsy.

CONTEXT: While numerous measures are available to assist physicians in assessing patients with cerebral palsy, there is a paucity of instruments that capture data relevant to osteopathic assessment. The lack of such tools limits the reach of research in key osteopathic indicators. METHODS: A structured objective form designed to assist osteopathic physicians in the evaluation of fascial restriction, restriction of spinal motion, and muscle spasticity was developed for use during osteopathic musculoskeletal structural examinations. Data were collected as part of a larger study investigating the effects of osteopathic manipulative treatment versus acupuncture in children with cerebral palsy. In the present study, confirmatory factor analysis was used to examine the relationships between fascial and spinal motion restrictions in addition to spasticity. RESULTS: In 57 children with spastic cerebral palsy, latent factors for fascial restrictions and spinal motion restriction fit the data well and both factors were correlated with a visual analog scale rating of the child's muscle spasticity. CONCLUSIONS: These findings provide preliminary evidence for the factorial and concurrent validity of fascial and spinal motion restrictions, demonstrating the benefits of an instrument for assessing the results of osteopathic musculoskeletal structural examinations.