636P Longitudinal insights into childhood onset facioscapulohumeral dystrophy: a five-year natural history study
Jeanette DijkstraHeather BoonAnne KoekkoekRianne J.M. GoselinkMaaike PelsmaS. Houwen-van OpstalNens van AlfenBaziel G.M. van EngelenNicol C. VoermansCorrie E. Erasmus
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Facioscapulohumeral muscular dystrophy
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April 26, 2018April 10, 2018Free AccessNeurodevelopmental needs in young boys with Duchenne Muscular Dystrophy: Observations from the CINRG DMD Natural History Study (P5.437)Mathula Thangarajh, Heather Gordish-Dressman, and Paula ClemensAuthors Info & AffiliationsApril 10, 2018 issue90 (15_supplement) Letters to the Editor
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Objective Facioscapulohumeral dystrophy (FSHD) is one of the most frequent heritable muscular dystrophies, with a large variety in age at onset and disease severity. The natural history and molecular characteristics of FSHD in childhood are incompletely understood. Our objective is to clinically and genetically characterize FSHD in childhood. Methods We performed a nationwide, single‐investigator, natural history study on FSHD in childhood. Results Multiple‐source recruitment resulted in 32 patients with FSHD (0–17 years), leading to an estimated prevalence of 1 in 100,000 children in The Netherlands. This series of 32 children with FSHD revealed a heterogeneous phenotype and genotype in childhood. The phenotypic hallmarks of FSHD in childhood are: facial weakness with normal or only mildly affected motor performance, decreased functional exercise capacity (6‐minute walk test), lumbar hyperlordosis, and increased echo intensity on muscle ultrasonography. In addition, pain and fatigue were frequent and patients experienced a lower quality of life compared to healthy peers. In contrast to the literature on early‐onset FSHD, systemic features such as hearing loss and retinal and cardiac abnormalities were infrequent and subclinical, and epilepsy and intellectual disability were absent. Genotypically, patients had a mean D4Z4 repeat array of 5 units (range, 2–9), and 14% of the mutations were de novo. Interpretation FSHD in childhood is more prevalent than previously known and the genotype resembles classic FSHD. Importantly, FSHD mainly affects functional exercise capacity and quality of life in children. As such, these results are paramount for counseling, clinical management, and stratification in clinical research. Ann Neurol 2018;84:635–645
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Multiple sclerosis (MS) has entered an era of immunomodulatory drug treatment, the impact of which on long-term disease progression remains controversial. The increasing use of these therapies has intensified our need to understand the true natural history of MS. The MS community is poised to establish whether the immunomodulatory drugs exhibit long-term benefits, with a suitable untreated natural history cohort likely the most practical and ethical comparator group. Thus, a thorough understanding of the natural history of MS is fundamental. In this review, we highlight recent advances in MS natural history over the last 5 years, with a focus on long-term population-based cohorts and factors associated with disease progression. Survival in MS has increased and longer times to irreversible disability have been reported in contemporary studies, indicating a slower accumulation of disability. Wide variation in the MS disease trajectory is evident within and between natural history studies, reflecting both methodologic considerations related to data collection and heterogeneity of disease activity. Recent publications have indicated that a younger age at disease onset is no longer indicative of a favorable outcome and further evidence supports the dissociation between relapses and long-term disability, although windows of opportunity may exist for some patients. We are now perhaps faced with our last chance to examine the true natural history of MS, so whether the reader is a practicing physician, health care provider, or researcher, or engaged in the pharmaceutical industry or in clinical trial design, recent advances in our understanding of the natural history of MS are of key significance.
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Degenerative cervical myelopathy (DCM) is the most frequent cause of spinal cord dysfunction and injury in the adult population and leads to significant loss of quality of life and economic impact from its associated medical care expenditures and loss of work. Surgical intervention is recommended for patients manifesting progressing neurological signs and symptoms of myelopathy, but the optimal management in individuals who have mild and clinically stable disease manifestations is controversial. Understanding the natural history of DCM is, thus, important in assessing patients and identifying those most appropriately indicated for surgical management. Despite the attempts to rigorously perform studies of the natural history of these patients, most published investigations suffer from methodological weaknesses or are underpowered to provide definitive answers. Investigations of particular patient subsets, however, provide some clinical guidance as to which patients stand most to benefit from surgery, and these may include those with lower baseline mJOA scores, evidence of segmental hypermobility, cord signal changes on MRI, abnormal somatosensory or motor-evoked potentials, or the presence of certain inflammatory markers. Clinicians should assess patients with mild myelopathy and those harboring asymptomatic cervical spinal cord compression individually when making treatment decisions and an understanding of the various factors that may influence natural history may aid in identifying those best indicated for surgery. Further investigations will likely identify how variables that affect natural history can be used in devising more precise treatment algorithms.
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Much controversy surrounds the issue of the natural history of hepatitis C virus (HCV) infection. Many authorities view the disease as inexorably progressive with a high probability of advancing over time to cirrhosis and occasionally hepatocellular carcinoma (HCC) and, therefore, likely to be responsible for causing death. Others regard chronic hepatitis C as having a variable outcome, the majority of infected persons not dying from the disease, but more likely from the comorbid conditions that so often accompany infection by this agent, or from more common medical conditions. Disagreements probably derive from the manner of conduct of the study and the populations studied. Efforts to determine natural history are handicapped by the primary characteristics of the disease, namely that its onset rarely is recognized and its course is prolonged exceedingly. Thus, different outcomes have come from retrospective rather than from prospective studies, but both have concluded that at least 20% of chronically infected adults develop cirrhosis within 20 years. More recent studies that used a retrospective/prospective approach, focusing largely on young infected individuals, have produced different results. Among these young people, particularly young women, spontaneous resolution of the viral infection is more common than previously thought and cirrhosis has been identified in 5% or fewer of them. The major failing for all groups studied, young and old, is that natural history studies have rarely exceeded the first 2 decades, so that outcome beyond this time is not known, other than through modeling. Several host-related and extraneous factors probably affect the natural history. (Hepatology 2002;36:S35-S46).
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We analyzed the natural history of amyotrophic lateral sclerosis in 277 patients. Our goal was to develop a better understanding of the clinical disease and thus improve the design of therapeutic trials. The Tufts Quantitative Neuromuscular Exam (TQNE) was used as the primary assessment instrument. Our analysis suggested that although more observations are desirable, six monthly TQNEs were adequate to establish the rate of disease progression. We observed a spectrum of deterioration rates without definable subgroups. The striking linearity of deterioration was confirmed. We found a high correlation between deterioration rates in arm and leg strength for individual patients, but a wide range between different patients. Sex and the age at clinical onset did not affect the deterioration rate. As compared with patients without a positive family history, those with other affected family members had a slower loss in arm but not leg strength. We propose that natural history controls can be used effectively in the design of ALS therapeutic trials.
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