Deborah J. Fox

Change in natural history of Duchenne muscular dystrophy with long-term corticosteroid treatment: implications for management.

In 2005, the American Academy of Neurology and the Child Neurology Society published a practice parameter, based primarily on studies that involved 6 to 18 months of treatment, indicating that prednisone has a beneficial effect on muscle strength and function in patients with Duchenne muscular dystrophy and recommended that corticosteroids be offered (prednisone 0.75 mg/kg/d and deflazacort 0.9 mg/kg/d) as treatment. Recent reports emphasize that longer term treatment with corticosteroids (greater than 3 years) produces important sustained benefits in neuromuscular function without causing major side effects. This review highlights these reports and indicates that long-term corticosteroid therapy (1) prolongs ambulation by 2 to 5 years, (2) reduces the need for spinal stabilization surgery, (3) improves cardiopulmonary function, (4) delays the need for noninvasive nasal ventilation, and (5) increases survival and the quality of life of patients with Duchenne muscular dystrophy. Educational, vocational, and other social counseling is now a vital part of management for Duchenne muscular dystrophy.

Delayed Diagnosis in Duchenne Muscular Dystrophy: Data from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet)

OBJECTIVE To identify key factors for the delay in diagnosis of Duchenne muscular dystrophy (DMD) without known family history. STUDY DESIGN The cohort comes from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet), a multistate, multiple-source, population-based surveillance system that identifies and gathers information on all cases of Duchenne and Becker muscular dystrophy born since 1982. We analyzed medical records of 453 Duchenne and Becker muscular dystrophy boys to document the time course and steps taken to reach a definitive diagnosis. RESULTS Among 156 boys without known family history of DMD prior to birth, first signs or symptoms were noted at a mean age of 2.5 years. Concerns resulted in primary care provider evaluation of the child at a mean age of 3.6 years. Mean age at time of initial creatine kinase was 4.7 years. Mean age at definitive diagnosis of DMD was 4.9 years. CONCLUSIONS There is a delay of about 2.5 years between onset of DMD symptoms and the time of definitive diagnosis, unchanged over the previous 2 decades. This delay results in lost opportunities for timely genetic counseling and initiation of corticosteroid treatment. We recommend checking creatine kinase early in the evaluation of boys with unexplained developmental delay.

Prevalence of Duchenne and Becker Muscular Dystrophies in the United States

OBJECTIVE: To estimate prevalence of childhood-onset Duchenne and Becker muscular dystrophies (DBMD) in 6 sites in the United States by race/ethnicity and phenotype (Duchenne muscular dystrophy [DMD] or Becker muscular dystrophy [BMD]). METHODS: In 2002, the Centers for Disease Control and Prevention established the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) to conduct longitudinal, population-based surveillance and research of DBMD in the United States. Six sites conducted active, multiple-source case finding and record abstraction to identify MD STARnet cases born January 1982 to December 2011. We used cross-sectional analyses to estimate prevalence of DBMD per 10 000 boys, ages 5 to 9 years, for 4 quinquennia (1991–1995, 1996–2000, 2001–2005, and 2006–2010) and prevalence per 10 000 male individuals, ages 5 to 24 years, in 2010. Prevalence was also estimated by race/ethnicity and phenotype. RESULTS: Overall, 649 cases resided in an MD STARnet site during ≥1 quinquennia. Prevalence estimates per 10 000 boys, ages 5 to 9 years, were 1.93, 2.05, 2.04, and 1.51, respectively, for 1991–1995, 1996–2000, 2001–2005, and 2006–2010. Prevalence tended to be higher for Hispanic individuals than non-Hispanic white or black individuals, and higher for DMD than BMD. In 2010, prevalence of DBMD was 1.38 per 10 000 male individuals, ages 5 to 24 years. CONCLUSIONS: We present population-based prevalence estimates for DBMD in 6 US sites. Prevalence differed by race/ethnicity, suggesting potential cultural and socioeconomic influences in the diagnosis of DBMD. Prevalence also was higher for DMD than BMD. Continued longitudinal surveillance will permit us to examine racial/ethnic and socioeconomic differences in treatment and outcomes for MD STARnet cases.

Use of Corticosteroids in a Population-Based Cohort of Boys With Duchenne and Becker Muscular Dystrophy

The use of corticosteroids for treatment of Duchenne and Becker muscular dystrophy in clinical practice from 1991 through 2005 was reviewed in a large population-based cohort (MD STARnet) of boys in 4 regional sites and 6 clinics of the United States. Corticosteroid use increased from 20% (11 of 56 individuals) in 1991 to 44% (93 of 218 individuals) in 2005. Average use varied by site and ranged from 15% to 49%. The median age of corticosteroid initiation was 6.9 years (range, 3.7-17.4 years). Dosage and growth information was available for 102 participants and showed a median dose as 0.729 mg/kg for prednisone and 0.831 mg/kg for deflazacort. T. The most common reasons that corticosteroids were discontinued included weight gain, behavioral side effects, and loss of ambulation, resulting in full-time wheelchair use. Substantial variations in clinical practice were identified among study sites.

Population-based microcephaly surveillance in the United States, 2009 to 2013: An analysis of potential sources of variation

BACKGROUND Congenital microcephaly has been linked to maternal Zika virus infection. However, ascertaining infants diagnosed with microcephaly can be challenging. METHODS Thirty birth defects surveillance programs provided data on infants diagnosed with microcephaly born 2009 to 2013. The pooled prevalence of microcephaly per 10,000 live births was estimated overall and by maternal/infant characteristics. Variation in prevalence was examined across case finding methods. Nine programs provided data on head circumference and conditions potentially contributing to microcephaly. RESULTS The pooled prevalence of microcephaly was 8.7 per 10,000 live births. Median prevalence (per 10,000 live births) was similar among programs using active (6.7) and passive (6.6) methods; the interdecile range of prevalence estimates was wider among programs using passive methods for all race/ethnicity categories except Hispanic. Prevalence (per 10,000 live births) was lowest among non-Hispanic Whites (6.5) and highest among non-Hispanic Blacks and Hispanics (11.2 and 11.9, respectively); estimates followed a U-shaped distribution by maternal age with the highest prevalence among mothers <20 years (11.5) and ≥40 years (13.2). For gestational age and birth weight, the highest prevalence was among infants <32 weeks gestation and infants <1500 gm. Case definitions varied; 41.8% of cases had an HC ≥ the 10th percentile for sex and gestational age. CONCLUSION Differences in methods, population distribution of maternal/infant characteristics, and case definitions for microcephaly can contribute to the wide range of observed prevalence estimates across individual birth defects surveillance programs. Addressing these factors in the setting of Zika virus infection can improve the quality of prevalence estimates. Birth Defects Research (Part A) 106:972-982, 2016.

Corticosteroid Treatments in Males With Duchenne Muscular Dystrophy: Treatment Duration and Time to Loss of Ambulation.

This population-based study examines the association between corticosteroid treatment and time to loss of ambulation, stratifying by treatment duration (short: 0.25-3 years, long: >3 years), among 477 Duchenne muscular dystrophy cases identified by the Muscular Dystrophy Surveillance Tracking and Research Network (MDSTARnet). Those cases who received short-term corticosteroid treatment had a time to loss of ambulation that was 0.8 years shorter (t test) and an annual risk of losing ambulation 77% higher than the untreated (Cox regression). Conversely, cases who received long-term corticosteroid treatment had a time to loss of ambulation that was 2 years longer and an annual risk of losing ambulation 82% lower than the untreated, up to age 11 years; after which the risks were not statistically different. The relationship of corticosteroids and time to loss of ambulation is more complex than depicted by previous studies limited to treatment responders or subjects who lost ambulation during study follow-up.

Issues in Estimating the Prevalence of Fetal Alcohol Syndrome: Examination of 2 Counties in New York State

OBJECTIVE. Two demographically similar counties included in the New York Fetal Alcohol Syndrome Surveillance Network had very different prevalence rates. This study examined the components of the surveillance in an attempt to discover the reasons for this discrepancy. METHODS. Erie County and Monroe County were the 2 most populous counties included in the New York Fetal Alcohol Syndrome Surveillance Network. Erie County includes Buffalo, the second largest city in New York State, and Monroe County includes Rochester, the third largest city. Multiple sources of ascertainment included birth defect surveillance systems, genetic clinics, and early intervention programs. The case definition was based on the Institute of Medicine criteria of an abnormality in each of the following 3 areas: facial features, central nervous system, and growth. RESULTS. Children born in Erie County or Monroe County between 1995 and 1999 were included. The fetal alcohol syndrome prevalence rates in these 2 counties were 0.90 cases per 1000 births and 0.21 cases per 1000 births, respectively. The 2 counties were demographically similar and had similar rates of binge drinking among women of childbearing age. There was less participation in the surveillance system by sources in Monroe County. Erie County had a very active clinician with a specialized fetal alcohol syndrome clinic. CONCLUSIONS. The participation of clinicians in one county, especially one with expertise in fetal alcohol syndrome, was the most likely explanation for the differences in prevalence rates between the counties.

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.

Trends With Corticosteroid Use in Males With Duchenne Muscular Dystrophy Born 1982-2001

This study examines trends in corticosteroid use for males with Duchenne muscular dystrophy by birth year, race/ethnicity, and knowledge of Duchenne muscular dystrophy family history. Firstborn males (n = 521) selected from a population-based surveillance system of Duchenne muscular dystrophy were analyzed using Kaplan Meier and regression methods. Comparing males born 1982 to 1986 with males born 1997 to 2001, steroid use increased from 54% to 72% and mean age at steroid initiation decreased from 8.2 to 7.1 years. Hispanics and non-Hispanic Black males used steroids less frequently and delayed initiation compared to white males. Compared to males without a Duchenne muscular dystrophy family history, males with known family history were half as likely to use steroids. Duration of steroid use increased over time and age at initiation decreased. Racial/ethnic disparities exist for steroid use and should be addressed to improve outcome and quality of life for boys with Duchenne muscular dystrophy.

Respiratory Care Received by Individuals With Duchenne Muscular Dystrophy From 2000 to 2011

BACKGROUND: Duchenne muscular dystrophy (DMD) causes progressive respiratory muscle weakness and decline in function, which can go undetected without monitoring. DMD respiratory care guidelines recommend scheduled respiratory assessments and use of respiratory assist devices. To determine the extent of adherence to these guidelines, we evaluated respiratory assessments and interventions among males with DMD in the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) from 2000 to 2011. METHODS: MD STARnet is a population-based surveillance system that identifies all individuals born during or after 1982 residing in Arizona, Colorado, Georgia, Hawaii, Iowa, and western New York with Duchenne or Becker muscular dystrophy. We analyzed MD STARnet respiratory care data for non-ambulatory adolescent males (12–17 y old) and men (≥18 y old) with DMD, assessing whether: (1) pulmonary function was measured twice yearly; (2) awake and asleep hypoventilation testing was performed at least yearly; (3) home mechanical insufflation-exsufflation, noninvasive ventilation, and tracheostomy/ventilators were prescribed; and (4) pulmonologists provided evaluations. RESULTS: During 2000–2010, no more than 50% of both adolescents and men had their pulmonary function monitored twice yearly in any of the years; 67% or fewer were assessed for awake and sleep hypoventilation yearly. Although the use of mechanical insufflation-exsufflation and noninvasive ventilation is probably increasing, prior use of these devices did not prevent all tracheostomies, and at least 18 of 29 tracheostomies were performed due to acute respiratory illnesses. Fewer than 32% of adolescents and men had pulmonologist evaluations in 2010–2011. CONCLUSIONS: Since the 2004 publication of American Thoracic Society guidelines, there have been few changes in pulmonary clinical practice. Frequencies of respiratory assessments and assist device use among males with DMD were lower than recommended in clinical guidelines. Collaboration of respiratory therapists and pulmonologists with clinicians caring for individuals with DMD should be encouraged to ensure access to the full spectrum of in-patient and out-patient pulmonary interventions.