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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.
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Enfermedades Virales del Sistema Nervioso Central , Infecciones por Enterovirus , Mielitis , Enfermedades Neuromusculares , Niño , Humanos , Mielitis/diagnóstico , Mielitis/terapia , Enfermedades Neuromusculares/diagnóstico , Enfermedades Neuromusculares/terapia , Enfermedades Virales del Sistema Nervioso Central/diagnóstico , Enfermedades Virales del Sistema Nervioso Central/terapia , Estudios Retrospectivos , Infecciones por Enterovirus/diagnóstico , Infecciones por Enterovirus/terapiaRESUMEN
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.
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Enfermedades Virales del Sistema Nervioso Central/diagnóstico por imagen , Enfermedades Virales del Sistema Nervioso Central/rehabilitación , Infecciones por Enterovirus/epidemiología , Hipotonía Muscular , Debilidad Muscular , Mielitis/diagnóstico por imagen , Mielitis/rehabilitación , Enfermedades Neuromusculares/diagnóstico por imagen , Enfermedades Neuromusculares/rehabilitación , Enfermedades Virales del Sistema Nervioso Central/líquido cefalorraquídeo , Enfermedades Virales del Sistema Nervioso Central/virología , Niño , Infecciones por Enterovirus/líquido cefalorraquídeo , Infecciones por Enterovirus/complicaciones , Salud Global , Humanos , Imagen por Resonancia Magnética , Hipotonía Muscular/etiología , Debilidad Muscular/etiología , Mielitis/líquido cefalorraquídeo , Mielitis/virología , Enfermedades Neuromusculares/líquido cefalorraquídeo , Enfermedades Neuromusculares/virología , Evaluación del Resultado de la Atención al PacienteRESUMEN
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.
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Distrofia Muscular de Duchenne , Escoliosis , Corticoesteroides/uso terapéutico , Humanos , Masculino , Distrofia Muscular de Duchenne/complicaciones , Distrofia Muscular de Duchenne/tratamiento farmacológico , Distrofia Muscular de Duchenne/epidemiología , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Escoliosis/complicaciones , Escoliosis/diagnóstico por imagen , Escoliosis/epidemiologíaRESUMEN
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.
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Parálisis Cerebral , Incontinencia Urinaria , Humanos , Femenino , Masculino , Niño , Preescolar , Rizotomía/métodos , Espasticidad Muscular/etiología , Espasticidad Muscular/cirugía , Raíces Nerviosas Espinales/diagnóstico por imagen , Raíces Nerviosas Espinales/cirugía , Parálisis Cerebral/cirugía , Médula Espinal/diagnóstico por imagen , Médula Espinal/cirugía , Incontinencia Urinaria/etiología , Resultado del TratamientoRESUMEN
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.
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Cuidadores , Distrofia Muscular de Duchenne , Niño , Femenino , Humanos , Masculino , Distrofia Muscular de Duchenne/complicaciones , Calidad de Vida , Encuestas y Cuestionarios , CaminataRESUMEN
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.
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Distrofina/genética , Limitación de la Movilidad , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/fisiopatología , Adolescente , Corticoesteroides/uso terapéutico , Niño , Deambulación Dependiente , Progresión de la Enfermedad , Exones , Duplicación de Gen , Humanos , Masculino , Distrofia Muscular de Duchenne/tratamiento farmacológico , Mutación Puntual , Modelos de Riesgos Proporcionales , Eliminación de Secuencia , Silla de RuedasRESUMEN
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.
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Toxinas Botulínicas Tipo A/uso terapéutico , Parálisis Cerebral/tratamiento farmacológico , Espasticidad Muscular/tratamiento farmacológico , Fármacos Neuromusculares/uso terapéutico , Extremidad Superior/fisiopatología , Adolescente , Toxinas Botulínicas Tipo A/efectos adversos , Parálisis Cerebral/fisiopatología , Niño , Preescolar , Método Doble Ciego , Femenino , Humanos , Inyecciones Intramusculares , Masculino , Espasticidad Muscular/fisiopatología , Fármacos Neuromusculares/efectos adversos , Resultado del TratamientoRESUMEN
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.
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Distrofia Muscular de Duchenne/patología , Distrofia Muscular de Duchenne/fisiopatología , Disfunción Ventricular Izquierda/patología , Disfunción Ventricular Izquierda/fisiopatología , Adolescente , Adulto , Niño , Preescolar , Estudios de Cohortes , Ecocardiografía , Glucocorticoides/uso terapéutico , Humanos , Lactante , Recién Nacido , Masculino , Distrofia Muscular de Duchenne/complicaciones , Distrofia Muscular de Duchenne/tratamiento farmacológico , Volumen Sistólico , Adulto JovenRESUMEN
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.
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Cuidadores/psicología , Recursos en Salud , Modelos Psicológicos , Distrofia Muscular de Duchenne/psicología , Distrofia Muscular de Duchenne/terapia , Calidad de Vida/psicología , Apoyo Social , Estrés Psicológico/complicaciones , Adaptación Psicológica , Adolescente , Adulto , Niño , Preescolar , Comorbilidad , Femenino , Humanos , Lactante , Control Interno-Externo , Acontecimientos que Cambian la Vida , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Increasingly long and complex informed consents have yielded studies demonstrating comparatively low participant comprehension and satisfaction with traditional face-to-face approaches. In parallel, interest in electronic consents for clinical and research genomics has steadily increased, yet limited data are available for trio-based genomic discovery studies. We describe the design, development, implementation, and validation of an electronic iConsent application for trio-based genomic research deployed to support genomic studies of cerebral palsy. iConsent development incorporated stakeholder perspectives including researchers, patient advocates, institutional review board members, and genomic data-sharing considerations. The iConsent platform integrated principles derived from prior electronic consenting research and elements of multimedia learning theory. Participant comprehension was assessed in an interactive teachback format. The iConsent application achieved nine of ten proposed desiderata for effective patient-focused electronic consenting for genomic research. Overall, participants demonstrated high comprehension and retention of key human subjects' considerations. Enrollees reported high levels of satisfaction with the iConsent, and we found that participant comprehension, iConsent clarity, privacy protections, and study goal explanations were associated with overall satisfaction. Although opportunities exist to optimize iConsent, we show that such an approach is feasible, can satisfy multiple stakeholder requirements, and can realize high participant satisfaction and comprehension while increasing study reach.
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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.
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Crecimiento , Distrofia Muscular de Duchenne/fisiopatología , Estatura , Índice de Masa Corporal , Peso Corporal , Niño , Preescolar , Humanos , Masculino , Estudios RetrospectivosRESUMEN
OBJECTIVE: To assess whether acute findings of cerebral arteriopathy, large infarct, and acutely elevated plasma D-dimer levels are independently prognostic of poor long-term neurologic outcome as measured at ≥ 1 year post-event in children with arterial ischemic stroke (AIS). STUDY DESIGN: Sixty-one patients with childhood-onset (ie, >28 days of life) AIS were enrolled in a single-institution cohort study at Children's Hospital Colorado between February 2006 and June 2011. Data on demographic and diagnostic characteristics, antithrombotic treatments, and outcomes were systematically collected. RESULTS: Cerebral arteriopathy and D-dimer levels >500 ng/mL (a measure of coagulation activation) were identified acutely in 41% and 31% of the cohort, respectively. Anticoagulation was administered in the acute period post-event in 40% of the children, in the subacute period in 43%, and in the chronic period in 28%. When not receiving anticoagulation, patients were routinely treated with aspirin 2-5 mg/kg once daily for a minimum of 1 year. Death, major bleeding (including intracranial hemorrhage), and recurrent AIS were infrequent. The Pediatric Stroke Outcome Measure at 1 year demonstrated poor outcome in 54% of the children. Acute cerebral arteriopathy and elevated D-dimer level were identified as putative prognostic factors for poor outcome; after adjustment for D-dimer, arteriopathy was an independent prognostic indicator (OR, 19.0; 95% CI, 1.6-229.8; P = .02). CONCLUSION: Arteriopathy and coagulation activation are highly prevalent in the acute period of childhood AIS. Although recurrent AIS and intracranial hemorrhage were infrequent in our cohort, one-half of children experienced a poor neurologic outcome at 1 year, the risk of which was increased by acute arteriopathy. Substantiation of these findings in multi-institutional cohort studies is warranted, toward risk stratification in childhood-onset AIS.
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Trastornos de la Coagulación Sanguínea/epidemiología , Enfermedades Arteriales Cerebrales/diagnóstico , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Fibrinolíticos/uso terapéutico , Accidente Cerebrovascular/diagnóstico , Trastornos de la Coagulación Sanguínea/complicaciones , Enfermedades Arteriales Cerebrales/complicaciones , Enfermedades Arteriales Cerebrales/tratamiento farmacológico , Estudios de Cohortes , Colorado , Femenino , Fibrinolíticos/efectos adversos , Humanos , Lactante , Masculino , Pronóstico , Recurrencia , Factores de Riesgo , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/tratamiento farmacológico , Resultado del TratamientoRESUMEN
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.
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Parálisis Cerebral , Lipoma , Traumatismos de la Médula Espinal , Parálisis Cerebral/complicaciones , Niño , Preescolar , Femenino , Marcha , Humanos , Lipoma/complicaciones , Lipoma/cirugía , Espasticidad Muscular/etiología , Espasticidad Muscular/cirugía , Rizotomía , Traumatismos de la Médula Espinal/complicaciones , Resultado del TratamientoRESUMEN
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.
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Toxinas Botulínicas Tipo A , Fármacos Neuromusculares , Fisiatras , Tortícolis , Niño , Consenso , Humanos , Espasticidad Muscular/tratamiento farmacológico , Fármacos Neuromusculares/uso terapéutico , Tortícolis/tratamiento farmacológico , Resultado del TratamientoRESUMEN
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.
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Toxinas Botulínicas Tipo A , Parálisis Cerebral , Fármacos Neuromusculares , Niño , Humanos , Fármacos Neuromusculares/uso terapéutico , Parálisis Cerebral/tratamiento farmacológico , Resultado del Tratamiento , Toxinas Botulínicas Tipo A/uso terapéutico , Espasticidad Muscular/tratamiento farmacológico , Extremidad SuperiorRESUMEN
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.
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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.
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Toxinas Botulínicas/uso terapéutico , Fármacos Neuromusculares/uso terapéutico , Enfermedades Neuromusculares/tratamiento farmacológico , Uso Fuera de lo Indicado , Niño , Humanos , Inyecciones Intramusculares , Espasticidad Muscular/tratamiento farmacológicoRESUMEN
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.
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Distrofias Musculares/epidemiología , Vigilancia en Salud Pública , Adolescente , Edad de Inicio , Niño , Preescolar , Humanos , Lactante , Estudios Longitudinales , Distrofias Musculares/terapia , Prevalencia , Enfermedades Raras/epidemiología , Enfermedades Raras/terapia , Estados Unidos/epidemiología , Adulto JovenRESUMEN
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.
RESUMEN
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.