Challenges in the Clinical Recognition of Acute Flaccid Myelitis and its Implications.

OBJECTIVES: To explore the challenges in diagnosing acute flaccid myelitis (AFM) and evaluate clinical features and treatment paradigms associated with under recognition. STUDY DESIGN: This was a retrospective multicenter study of pediatric patients (≤18 years) who were diagnosed with AFM from 2014 to 2018 using the Centers for Disease Control and Prevention's case definition. RESULTS: In 72% of the cases (126 of 175), AFM was not considered in the initial differential diagnosis (n = 108; 61.7%) and/or the patient was not referred for acute care (n = 90; 51.4%) at the initial clinical encounter, and this did not improve over time. Although many features of the presentation were similar in those initially diagnosed with AFM and those who were not; preceding illness, constipation, and reflexes differed significantly between the 2 groups. Patients with a non-AFM initial diagnosis more often required ventilatory support (26.2% vs 12.2%; OR, 0.4; 95% CI, 0.2-1.0; P = .05). These patients received immunomodulatory treatment later (3 days vs 2 days after neurologic symptom onset; 95% CI, -2 to 0; P = .05), particularly intravenous immunoglobulin (5 days vs 2 days; 95% CI, -4 to -2; P < .001). CONCLUSIONS: Delayed recognition of AFM is concerning because of the risk for respiratory decompensation and need for intensive care monitoring. A non-AFM initial diagnosis was associated with delayed treatment that could have a clinical impact, particularly as new treatment options emerge.

Goal Attainment after Treatment with Abobotulinumtoxina and a Tailored Home Therapy Programme in Children with Upper Limb Spasticity: Descriptive, Exploratory Analysis of a Large Randomized, Controlled Study

OBJECTIVE: This exploratory analysis of a large, randomized, double-blind study (NCT02106351) describes the effect of treatment with abobotulinumtoxinA followed by a tailored home exercises therapy programme in enabling children with upper limb spasticity due to cerebral palsy to achieve their functional goals using goal attainment scaling (GAS). METHODS: Children with cerebral palsy and spasticity in ≥ 1 upper limb received up to 4 injection cycles of abobotulinumtoxinA (2 U/kg (cycle 1 only), 8U/kg and 16U/kg) into the elbow and wrist flexors and other upper limb muscles selected to support individual treatment goals. Children followed a home exercises therapy programme, which included stretches and exercises specifically chosen to facilitate goal achievement and engagement in activities. RESULTS: For cycle 1, most children had active function goals set as their primary goal (69.7% vs 19.2% passive function goals). GAS T- scores and goal responder rates at week 16 indicated that most types of primary goal were achieved at least as expected during cycle 1 (all groups). Primary goal GAS T-scores were generally maintained for the first 3 abobotulinumtoxinA treatment cycles. CONCLUSION: Most children with upper limb spasticity treated with repeat cycles of abobotulinumtoxinA supported by an individualized home exercises therapy programme achieved their functional goals.

Spinal cord tethering after selective dorsal rhizotomy below the conus medullaris.

BACKGROUND: Two techniques for selective dorsal rhizotomy (SDR) involve stimulating and sectioning nerve rootlets either below the conus medullaris or above the entrances to their respective dural root sleeves. In general, both techniques lead to sustained improvements in lower extremity spasticity with low complication rates. To our knowledge, spinal cord tethering has not been previously reported as a complication of SDR using either technique. METHODS: We review the presentation, treatment, and outcome of two patients who developed symptomatic spinal cord tethering after SDR below the conus. RESULTS: A 4-year-old male and a 6-year-old female each with a history of spastic diparetic cerebral palsy underwent L1-L2 osteoplastic laminectomy and SDR below the conus. Both surgeries went well with no known complications. Both patients initially did well, with marked improvement in their tone and gait. There were no significant immediate postoperative bowel or bladder problems. The male patient presented 10 months after surgery with new-onset urinary incontinence. A urological evaluation was performed but no imaging was performed. He re-presented 8 months later with worsened urinary incontinence, new fecal incontinence, and worsened gait. An MRI showed signs of tethering, including a holocord syrinx. He underwent two untethering surgeries as well syrinx fenestration, and although his gait improved, it remained worse than it had been several months after surgery. The incontinence did not improve. The second patient also developed urinary incontinence a year after SDR. Due to our experience with the first patient, we obtained an MRI immediately and found evidence of tethering. She underwent untethering and her incontinence improved. CONCLUSION: We report two cases of spinal cord tethering after SDR below the conus, a previously unreported complication. It is important to realize that this complication can occur after SDR.

Selective dorsal rhizotomy for spasticity associated with spinal cord injury sustained during surgery for spinal lipomatous malformation: A case report.

Selective dorsal rhizotomy (SDR) was used to treat lower extremity spasticity in an ambulatory 7-year-old girl with a history of a T10 spinal lipoma. The spasticity was the result of an AIS D spinal cord injury (SCI) suffered during untethering surgery at age 2 years. After SDR and a course of intensive inpatient rehabilitation, the patient's gait improved markedly. To the authors' knowledge, this is the first published case of SDR as a treatment for spasticity in a patient with a spinal lipomatous malformation.

A consensus statement on the use of botulinum toxin in pediatric patients.

Botulinum toxin has been used in medicine for the past 30 years. However, there continues to be controversy about the appropriate uses and dosing, especially in the pediatric population. A panel of nine pediatric physiatrists from different regions and previous training programs in the United States were nominated based on institutional reputation and botulinum toxin (BoNT) experience. Based on a review of the current literature, the goal was to provide the rationale for recommendations on the administration of BoNT in the pediatric population. The goal was not only to review safety, dosing, and injection techniques but also to develop a consensus on the appropriate uses in the pediatric population. In addition to upper and lower limb spasticity, the consensus also provides recommendations for congenital muscular torticollis, cervical dystonia, sialorrhea, and brachial plexus palsies.

A population-based study of scoliosis among males diagnosed with a dystrophinopathy identified by the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet).

INTRODUCTION/AIMS: Scoliosis is a common comorbidity among individuals diagnosed with a dystrophinopathy. We examined associations between clinical predictors and scoliosis in childhood-onset dystrophinopathy. METHODS: The progression and treatment of scoliosis were obtained from data collected by the US population-based Muscular Dystrophy Surveillance, Tracking, and Research Network. Associations between loss of independent ambulation (LoA) and corticosteroid use and scoliosis outcomes (ages at or exceeding Cobb angle thresholds [10°, 20°, 30°]; surgery) were estimated using Kaplan-Meier curve estimation and extended Cox regression modeling. RESULTS: We analyzed curvature data for 513 of 1054 individuals ascertained. Overall, approximately one-half had at least one radiograph and one-quarter had a curvature of at least 20°. The average maximum curvature was 25.0° (SD = 21.5°) among all individuals and 42.8° (SD = 18.8°) among those recommended for surgery. Higher adjusted hazards ratio of curvature (aHR(curvature) [95% confidence interval]) were found among individuals with LoA compared to those without LoA (aHR(10)  = 6.2 [4.4, 8.7], aHR(20)  = 15.3 [7.4, 31.7], aHR(30)  = 31.6 [7.7, 128.9]), among individuals who did not use corticosteroids compared to those who did (aHR(10)  = 1.2 [0.9, 1.7], aHR(20)  = 1.8 [1.1, 2.7], aHR(30)  = 2.3 [1.3, 4.0]), and among non-ambulatory individuals who used corticosteroids after LoA compared to those who did not (aHR(10)  = 1.8 [1.2, 2.8], aHR(20)  = 1.6 [1.0, 2.6], aHR(30)  = 3.6 [1.6, 7.9]). Scoliosis surgery among individuals with LoA who did not use corticosteroids was more than double compared to those who used (aHR = 2.3 [1.3, 4.2]). DISCUSSION: Our retrospective observational study suggests corticosteroids may delay spinal curvature progression and need for scoliosis surgery. Continuing corticosteroids after LoA also showed potential benefits of delaying curvature progression, additional studies are needed to confirm this finding or address the magnitude of benefit.

Muscle Selection and Dosing in a Phase 3, Pivotal Study of AbobotulinumtoxinA Injection in Upper Limb Muscles in Children With Cerebral Palsy.

Background: Guidelines recommend botulinum toxin-A in pediatric upper limb spasticity as part of routine practice. Appropriate dosing is a prerequisite for treatment success and it is important that injectors have an understanding on how to tailor dosing within a safe and effective range. We report upper limb dosing data from a phase 3 study of abobotulinumtoxinA injections in children with cerebral palsy. Methods: This was a double-blind, repeat-treatment study (NCT02106351). In Cycle 1, children were randomized to abobotulinumtoxinA at 2 U/kg control dose or clinically relevant 8 U/kg or 16 U/kg doses. Doses were divided between the primary target muscle group (PTMG, wrist or elbow flexors) and additional muscles tailored to clinical presentation. During Cycles 2-4, children received doses of 8 U/kg or 16 U/kg and investigators could change the PTMG and other muscles to be injected. Injection of muscles in the other upper limb and lower limbs was also permitted in cycles 2-4, with the total body dose not to exceed 30 U/kg or 1,000 U (whichever was lower) in the case of upper and lower limb treatment. Results: 212 children were randomized, of which 210 received ≥1 abobotulinumtoxinA injection. Per protocol, the elbow and wrist flexors were the most commonly injected upper limb muscles. Across all 4 cycles, the brachialis was injected in 89.5% of children (dose range 0.8-6 U/kg), the brachioradialis in 83.8% (0.4-3 U/kg), the flexor carpi ulnaris in 82.4% (0.5-3 U/kg) and the flexor carpi radialis in 79.5% (0.5-4 U/kg). Other frequently injected upper limb muscles were the pronator teres(70.0%, 0.3-3 U/kg). adductor pollicis (54.3%, 0.3-1 U/kg), pronator quadratus (44.8%, 0.1-2 U/kg), flexor digitorum superficialis (39.0%, 0.5-4 U/kg), flexor digitorum profundus (28.6%, 0.5-2 U), flexor pollicis brevis/opponens pollicis (27.6%, 0.3-1 U/kg) and biceps (27.1%, 0.5-6 U/kg). AbobotulinumtoxinA was well-tolerated at these doses; muscular weakness was reported in 4.3% of children in the 8 U/kg group and 5.7% in the 16 U/kg group. Conclusions: These data provide information on the pattern of injected muscles and dose ranges used in this study, which were well-tolerated. Per protocol, most children received injections into the elbow and wrist flexors. However, there was a wide variety of other upper limb muscles injected as physicians tailored injection patterns to clinical need.

Labor market participation and productivity costs for female caregivers of minor male children with Duchenne and Becker muscular dystrophies.

INTRODUCTION/AIMS: Duchenne and Becker muscular dystrophies (DBMD) are X-linked neuromuscular disorders characterized by progressive muscle weakness, leading to decreased mobility and multisystem complications. We estimate productivity costs attributable to time spent by a parent caring for a male child under the age of 18 y with DBMD, with particular focus on female caregivers of boys with Duchenne muscular dystrophy (DMD) who have already lost ambulation. METHODS: Primary caregivers of males with DBMD in the Muscular Dystrophy Surveillance and Research Tracking Network (MD STARnet) were surveyed during 2011-2012 on family quality of life measures, including labor market outcomes. Of 211 respondents, 96 female caregivers of boys with DBMD were matched on state, year of survey, respondent's age, child's age, and number of minor children with controls constructed from Current Population Survey extracts. Regression analysis was used to estimate labor market outcomes and productivity costs. RESULTS: Caregivers of boys with DBMD worked 296 h less per year on average than caregivers of unaffected children, translating to a $8816 earnings loss in 2020 U.S. dollars. Caregivers of boys with DMD with ≥4 y of ambulation loss had a predicted loss in annualized earnings of $23,995, whereas caregivers of boys with DBMD of the same ages who remained ambulatory had no loss of earnings. DISCUSSION: Female caregivers of non-ambulatory boys with DMD face additional household budget constraints through income loss. Failure to include informal care costs in economic studies could understate the societal cost-effectiveness of strategies for managing DMD that might prolong ambulation.

Efficacy and safety of abobotulinumtoxinA for upper limb spasticity in children with cerebral palsy: a randomized repeat-treatment study.

AIM: To assess the efficacy and safety of repeat abobotulinumtoxinA injections in reducing upper limb spasticity in children with cerebral palsy (CP). METHOD: This was a double-blind, repeat-cycle study (NCT02106351) in children with CP (2-17y). Children were randomized to receive 2U/kg (control), 8U/kg, or 16U/kg abobotulinumtoxinA injections into the target muscle group (wrist or elbow flexors) and additional muscles alongside occupational therapy via a home-exercise therapy program (HETP; minimum five 15min sessions/wk). Children received 8U/kg or 16U/kg plus HETP in cycles 2 to 4. RESULTS: During cycle 1, 210 children (126 males, 84 females; mean age [SD] 9y [4y 5mo], range 2-17y; n=70/group) had at least one upper limb abobotulinumtoxinA injection and 209 complied with the HETP. At week 6 of cycle 1, children in the 8U/kg or 16U/kg groups had significantly lower Modified Ashworth scale scores versus the 2U/kg group (primary outcome: treatment differences of -0.4 [p=0.012] and -0.7 [p<0.001] respectively). All groups improved on Physician Global Assessment and children in all groups achieved their treatment goals at least as expected. Therapeutic benefits were sustained during cycles 2 to 4; muscular weakness was the only treatment-related adverse event reported in at least one child/group (4.3% and 5.7% vs 1.4% respectively). INTERPRETATION: Treatment with 8U/kg or 16U/kg abobotulinumtoxinA significantly reduced upper limb spasticity versus the 2U/kg control dose. Therapeutic benefits of abobotulinumtoxinA plus HETP were sustained with repeat treatment cycles. WHAT THIS PAPER ADDS: AbobotulinumtoxinA injections significantly reduced upper limb spasticity in children with cerebral palsy. Children treated with abobotulinumtoxinA and targeted home exercises showed global improvement and goal attainment. Benefits were sustained over 1 year with repeat cycles of abobotulinumtoxinA and home exercises. AbobotulinumtoxinA injections into the upper limb were well tolerated over 1 year.

Acute flaccid myelitis: cause, diagnosis, and management.

Acute flaccid myelitis (AFM) is a disabling, polio-like illness mainly affecting children. Outbreaks of AFM have occurred across multiple global regions since 2012, and the disease appears to be caused by non-polio enterovirus infection, posing a major public health challenge. The clinical presentation of flaccid and often profound muscle weakness (which can invoke respiratory failure and other critical complications) can mimic several other acute neurological illnesses. There is no single sensitive and specific test for AFM, and the diagnosis relies on identification of several important clinical, neuroimaging, and cerebrospinal fluid characteristics. Following the acute phase of AFM, patients typically have substantial residual disability and unique long-term rehabilitation needs. In this Review we describe the epidemiology, clinical features, course, and outcomes of AFM to help to guide diagnosis, management, and rehabilitation. Future research directions include further studies evaluating host and pathogen factors, including investigations into genetic, viral, and immunological features of affected patients, host-virus interactions, and investigations of targeted therapeutic approaches to improve the long-term outcomes in this population.

Association of genetic mutations and loss of ambulation in childhood-onset dystrophinopathy.

BACKGROUND: Quantifying associations between genetic mutations and loss of ambulation (LoA) among males diagnosed with childhood-onset dystrophinopathy is important for understanding variation in disease progression and may be useful in clinical trial design. METHODS: Genetic and clinical data from the Muscular Dystrophy Surveillance, Tracking, and Research Network for 358 males born and diagnosed from 1982 to 2011 were analyzed. LoA was defined as the age at which independent ambulation ceased. Genetic mutations were defined by overall type (deletion/duplication/point mutation) and among deletions, those amenable to exon-skipping therapy (exons 8, 20, 44-46, 51-53) and another group. Cox proportional hazards regression modeling was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Mutation type did not predict time to LoA. Controlling for corticosteroids, Exons 8 (HR = 0.22; 95% CI = 0.08, 0.63) and 44 (HR = 0.30; 95% CI = 0.12, 0.78) were associated with delayed LoA compared to other exon deletions. CONCLUSIONS: Delayed LoA in males with mutations amenable to exon-skipping therapy is consistent with previous studies. These findings suggest that clinical trials including exon 8 and 44 skippable males should consider mutation information prior to randomization.

Out of the spasticity box: Off-label uses of botulinum toxin in children.

Botulinum toxin is frequently used as a therapeutic for a variety of non-FDA approved indications in children. This narrative literature review explores three off-label uses of botulinum toxin in pediatric conditions including congenital muscular torticollis, spastic trismus, and neonatal brachial plexus palsy. While more research is needed to establish treatment, dosing and localization guidelines for the use of botulinum toxin in these commonly treated conditions, available evidence is discussed.

Left ventricular dysfunction in Duchenne muscular dystrophy.

BACKGROUND: Duchenne muscular dystrophy is associated with progressive cardiorespiratory failure, including left ventricular dysfunction. METHODS AND RESULTS: Males with probable or definite diagnosis of Duchenne muscular dystrophy, diagnosed between 1 January, 1982 and 31 December, 2011, were identified from the Muscular Dystrophy Surveillance Tracking and Research Network database. Two non-mutually exclusive groups were created: patients with ≥2 echocardiograms and non-invasive positive pressure ventilation-compliant patients with ≥1 recorded ejection fraction. Quantitative left ventricular dysfunction was defined as an ejection fraction <55%. Qualitative dysfunction was defined as mild, moderate, or severe. Progression of quantitative left ventricular dysfunction was modelled as a continuous time-varying outcome. Change in qualitative left ventricle function was assessed by the percentage of patients within each category at each age. Forty-one percent (n = 403) had ≥2 ejection fractions containing 998 qualitative assessments with a mean age at first echo of 10.8 ± 4.6 years, with an average first ejection fraction of 63.1 ± 12.6%. Mean age at first echo with an ejection fraction <55 was 15.2 ± 3.9 years. Thirty-five percent (140/403) were non-invasive positive pressure ventilation-compliant and had ejection fraction information. The estimated rate of decline in ejection fraction from first ejection fraction was 1.6% per year and initiation of non-invasive positive pressure ventilation did not change this rate. CONCLUSIONS: In our cohort, we observed that left ventricle function in patients with Duchenne muscular dystrophy declined over time, independent of non-invasive positive pressure ventilation use. Future studies are needed to examine the impact of respiratory support on cardiac function.

A Review of MD STAR net's Research Contributions to Pediatric-Onset Dystrophinopathy in the United States; 2002-2017.

Population studies of rare disorders, such as Duchenne and Becker muscular dystrophies (dystrophinopathies), are challenging due to diagnostic delay and heterogeneity in disorder milestones. To address these challenges, the Centers for Disease Control and Prevention established the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STAR net) in 2002 in the United States. From 2002 to 2012, MD STAR net longitudinally tracked the prevalence, clinical, and health care outcomes of 1054 individuals born from 1982 to 2011 with pediatric-onset dystrophinopathy through medical record abstraction and survey data collection. This article summarizes 31 MD STAR net peer-reviewed publications. MD STAR net provided the first population-based prevalence estimates of childhood-onset dystrophinopathy in the United States. Additional publications provided insights into diagnostic delay, dystrophinopathy-specific growth charts, and health services use. Ongoing population-based surveillance continually improves our understanding of clinical and diagnostic outcomes of rare disorders.

Health Care Transition Experiences of Males with Childhood-onset Duchenne and Becker Muscular Dystrophy: Findings from the Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet) Health Care Transitions and Other Life Experiences Survey.

Introduction: As the proportion of males with Duchenne muscular dystrophy (DMD) surviving into adulthood increases, more information is needed regarding their health care transition planning, an essential process for adolescents and young adults with DMD. The objective of this study was to describe the health care transition experiences of a population of males living with Duchenne or Becker muscular dystrophy (DBMD). Methods: The eligible participants, identified through the Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet) surveillance project, were 16-31 years old and lived in Arizona, Colorado, Georgia, Iowa, or western New York (n=258). The MD STARnet Health Care Transitions and Other Life Experiences Survey was conducted in 2013 and administered online or in a telephone interview. Sixty-five males (25%) completed the survey. Among non-ambulatory males, response differences were compared by age group. Statistical comparisons were conducted using Fisher's exact test, or when appropriate, the Chisquare test. Results: Twenty-one percent of non-ambulatory males aged 16-18 years, 28% of non-ambulatory males aged 19-23 years, 25% of non-ambulatory males aged 24-30 years, and 18 ambulatory males had a written transition plan. Nineteen percent of non-ambulatory males aged 24-30 years had delayed or gone without needed health care in the past 12 months. Among non-ambulatory males aged 24-30 years, 75% had cardiology providers and 69% had pulmonology providers involved in their care in the past 12 months. Twentyeight percent of non-ambulatory males aged 19-23 years and 25% of non-ambulatory males aged 24-30 years reported that they did not receive health care or other services at least once because they were unable to leave their home. Non-ambulatory males aged 16-18 years (29%) were less likely to have ever discussed how to obtain or keep health insurance as they get older compared to non-ambulatory males aged 24-30 years (69%) (p <0.01). Discussion: This study identified potential barriers to the successful health care transition of males with DBMD. The results of this study may indicate a lack of targeted informational resources and education focused on supporting the transition of young men with DBMD as they age from adolescence into adulthood within the healthcare system. Future studies could determine the reasons for the potential barriers to health care and identify the optimal transition programs for males with DBMD. There are a few online resources on transition available to adolescents and young adults with special health care needs.

Bone Health and Endocrine Care of Boys with Duchenne Muscular Dystrophy: Data from the MD STARnet.

BACKGROUND: Patients with Duchenne muscular dystrophy (DMD) are at high risk of endocrine and bone health complications resulting from the high glucocorticoid (GC) doses used to treat this condition. There are limited data characterizing the clinical management of these complications. OBJECTIVE: To determine the frequency of bone health screening, endocrinologist evaluation, and use of endocrine and bone health pharmacotherapy in the clinical care of males with DMD. METHODS: A population based cohort study using data from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) was conducted. Clinical data was abstracted from the medical records of 683 males with DMD at five surveillance sites across the US. RESULTS: A DXA scan had been documented in 24% of cases; the percentage of cases with DXA varied across surveillance sites from 13% to 43%, p < 0.001. History of fracture and greater disease duration were associated with greater odds of having a DXA. Only 4.7% of cases had documentation of an endocrinologist evaluation. The frequency of documented endocrine and bone health pharmacotherapy use included calcium (42.8%), vitamin D (36.6%), bisphosphonates (13.3%), growth hormone (1.9%), testosterone (1.7%), insulin (1.2%), and metformin (0.3%)Conclusions:A low percentage of DMD males had record of DXA scan, endocrinologist evaluation, or treatment with endocrine or bone health pharmacotherapy. Endocrine and bone health care may represent an unmet need in the DMD population.

Muscular Dystrophy Surveillance, Tracking, and Research Network pilot: Population-based surveillance of major muscular dystrophies at four U.S. sites, 2007-2011.

BACKGROUND: For 10 years, the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) conducted surveillance for Duchenne and Becker muscular dystrophy (DBMD). We piloted expanding surveillance to other MDs that vary in severity, onset, and sources of care. METHODS: Our retrospective surveillance included individuals diagnosed with one of nine eligible MDs before or during the study period (January 2007-December 2011), one or more health encounters, and residence in one of four U.S. sites (Arizona, Colorado, Iowa, or western New York) at any time within the study period. We developed case definitions, surveillance protocols, and software applications for medical record abstraction, clinical review, and data pooling. Potential cases were identified by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes 359.0, 359.1, and 359.21 and International Classification of Diseases, Tenth Revision (ICD-10) codes G71.0 and G71.1. Descriptive statistics were compared by MD type. Percentage of MD cases identified by each ICD-9-CM code was calculated. RESULTS: Of 2,862 cases, 32.9% were myotonic, dystrophy 25.8% DBMD, 9.7% facioscapulohumeral MD, and 9.1% limb-girdle MD. Most cases were male (63.6%), non-Hispanic (59.8%), and White (80.2%). About, half of cases were genetically diagnosed in self (39.1%) or family (6.2%). About, half had a family history of MD (48.9%). The hereditary progressive MD code (359.1) was the most common code for identifying eligible cases. The myotonic code (359.21) identified 83.4% of eligible myotonic dystrophy cases (786/943). CONCLUSIONS: MD STARnet is the only multisite, population-based active surveillance system available for MD in the United States. Continuing our expanded surveillance will contribute important epidemiologic and health outcome information about several MDs.

Outcomes of Colorado children with acute flaccid myelitis at 1 year.

OBJECTIVE: We describe long-term functional, neurodiagnostic, and psychosocial outcomes of a cohort of 12 children from Colorado diagnosed with acute flaccid myelitis (AFM) in 2014. METHODS: Children were assessed every 3 months for 1 year or until clinical resolution. Assessments included neurologic examination, MRI, EMG/nerve conduction studies (NCS), functional measures (Assisting Hand Assessment, Hammersmith Functional Motor Scale), and Patient-Reported Outcomes Measurement Information System questionnaires. RESULTS: Eight of 12 children completed the study. Six of 8 had persistent motor deficits at 1 year; 2 demonstrated full recovery. Four were not enrolled, 2 of whom reported full recovery. The 6 affected were weakest in proximal muscles, showing minimal to no improvement and significant atrophy at 1 year. All patients improved in distal muscle groups. Cranial nerve dysfunction resolved in 2 of 5 and improved in all. Four of 5 showed progressive functional improvement at 6 and 12 months. Two of 8 reported pain at 1 year. Three of 8 reported depressive symptoms. Repeat MRI was performed in 7 of 8 children a median of 7 months after onset and showed significant improvement or normalization in all but one child. Repeat EMG/NCS was performed on 4 children a median of 8 months after onset and showed ongoing denervation and chronic reinnervation in 3 children with persistent deficits. CONCLUSIONS: At 1 year, children with AFM demonstrated functional gains but weakness persisted. EMG changes correlated with persistent deficits better than imaging. Despite improvements, AFM had substantial long-term functional effects on affected children.

Secondary Conditions Among Males With Duchenne or Becker Muscular Dystrophy.

Duchenne and Becker muscular dystrophy are X-linked neuromuscular disorders characterized by progressive muscle degeneration. Despite the involvement of multiple systems, secondary conditions among affected males have not been comprehensively described. Two hundred nine caregivers of affected males (aged 3-31 years) identified by the Muscular Dystrophy Surveillance, Tracking, and Research Network completed a mailed survey that included questions about secondary conditions impacting multiple body functions. The 5 most commonly reported conditions in males with Duchenne were cognitive deficits (38.4%), constipation (31.7%), anxiety (29.3%), depression (27.4%), and obesity (19.5%). Higher frequencies of anxiety, depression, and kidney stones were found among nonambulatory males compared to ambulatory males. Attention-deficit hyperactivity disorder (ADHD) was more common in ambulatory than nonambulatory males. These data support clinical care recommendations for monitoring of patients with Duchenne or Becker muscular dystrophy by a multidisciplinary team to prevent and treat conditions that may be secondary to the diagnosis.

Perceived quality of life among caregivers of children with a childhood-onset dystrophinopathy: a double ABCX model of caregiver stressors and perceived resources.

BACKGROUND: Duchenne and Becker muscular dystrophies, collectively referred to as dystrophinopathies, are recessive X-linked disorders characterized by progressive muscle weakness and ultimately cardiac and respiratory failure. Immediate family members are often primary caregivers of individuals with a dystrophinopathy. METHODS: We explored the impact of this role by inviting primary caregivers (n = 209) of males diagnosed with childhood-onset dystrophinopathy who were identified by the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) to complete a mailed questionnaire measuring perceived social support and stress, spirituality, and family quality of life (FQoL). Bivariate and multivariate analyses examined associations between study variables using the Double ABCX model as an analytic framework. RESULTS: Higher stressor pile-up was associated with lower perceived social support (r = -0.29, p < .001), availability of supportive family (r = -0.30, p < .001) or non-family (r = -0.19, p < .01) relationships, and higher perceived stress (r = 0.33, p < .001); but not with spirituality (r = -0.14, p > 0.05). FQoL was positively associated with all support measures (correlations ranged from: 0.25 to 0.58, p-values 0.01-0.001) and negatively associated with perceived stress and control (r = -0.49, p < .001). The association between stressor pile-up and FQoL was completely mediated through global perceived social support, supportive family relationships, and perceived stress and control; supportive non-family relationships did not remain statistically significant after controlling for other mediators. CONCLUSIONS: Findings suggest caregiver adaptation to a dystrophinopathy diagnosis can be optimized by increased perceived control, supporting family resources, and creation of a healthy family identity. Our findings will help identify areas for family intervention and guide clinicians in identifying resources that minimize stress and maximize family adaptation.