Ultrasound evaluation of fetal movements in pregnancies at risk for severe spinal muscular atrophy

Parra, Johanna; Martínez-Hernández, Rebeca; Also-Rallo, Eva; Alías, Laura; Barceló, Montserrat; Amenedo, Maria; Medina, Carmen; Senosiain, Raquel; Calaf, Joaquím; Baiget, Montserrat; Bernal, Sara; Tizzano, Eduardo F.

doi:10.1016/j.nmd.2010.09.010

Cited by 17 publications

(11 citation statements)

References 27 publications

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“…This would explain previous findings in type I SMA fetuses, such as the increase of apoptotic neurons in the spinal cord and the delay in muscle maturation . On the other hand, SMA fetuses are able to form active synapses, express choline acetyltransferase , and perform muscle movements indistinguishable from control fetuses . These facts, which are in apparent contradiction with our present results, could be explained by several factors, such as polyaxonal innervation, sprouting, a liquid fetal environment, an exquisite sensitivity of the fetus to respond to stimuli, or other unknown mechanisms that may partially compensate for the innervation defects in SMA at this stage of development.…”

Section: Discussioncontrasting

confidence: 99%

Synaptic defects in type I spinal muscular atrophy in human development

Martínez-Hernández

Bernal

Also-Rallo

et al. 2012

The Journal of Pathology

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Childhood spinal muscular atrophy is an autosomal recessive neuromuscular disorder caused by alterations in the Survival Motor Neuron 1 gene that triggers degeneration of motor neurons within the spinal cord. Spinal muscular atrophy is the second most common severe hereditary disease of infancy and early childhood. In the most severe cases (type I), the disease appears in the first months of life, suggesting defects in fetal development. However, it is not yet known how motor neurons, neuromuscular junctions, and muscle interact in the neuropathology of the disease. We report the structure of presynaptic and postsynaptic apparatus of the neuromuscular junctions in control and spinal muscular atrophy prenatal and postnatal human samples. Qualitative and quantitative data from confocal and electron microscopy studies revealed changes in acetylcholine receptor clustering, abnormal preterminal accumulation of vesicles, and aberrant ultrastructure of nerve terminals in the motor endplates of prenatal type I spinal muscular atrophy samples. Fetuses predicted to develop milder type II disease had a similar appearance to controls. Postnatal muscle of type I spinal muscular atrophy patients showed persistence of the fetal subunit of acetylcholine receptors, suggesting a delay in maturation of neuromuscular junctions. We observed that pathology in the severe form of the disease starts in fetal development and that a defect in maintaining the initial innervation is an early finding of neuromuscular dysfunction. These results will improve our understanding of the spinal muscular atrophy pathogenesis and help to define targets for possible presymptomatic therapy for this disease. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Section: Discussioncontrasting

confidence: 99%

Synaptic defects in type I spinal muscular atrophy in human development

Martínez-Hernández

Bernal

Also-Rallo

et al. 2012

The Journal of Pathology

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“…One hypothesis is a developmental defect in maturation as well as a postnatal retrograde dying-back degeneration of LMNs in SMN-deficient SMA [23]. Their observations in SMA fetuses support previous observations by Parra et al [24], who prospectively demonstrated normal fetal movements in the first trimester in those later determined via prenatal or postnatal diagnosis to be genetically affected.…”

Section: Recent Advances In Sma Pathophysiologysupporting

confidence: 76%

New Therapeutic Approaches to Spinal Muscular Atrophy

Lewelt

Newcomb

Swoboda

2011

Curr Neurol Neurosci Rep

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Bench to bedside progress has been widely anticipated for a growing number of neurodegenerative disorders. Of these, spinal muscular atrophy (SMA) is perhaps the best poised to capitalize on advances in targeted therapeutics development over the next few years. Several laboratories have achieved compelling success in SMA animal models using sophisticated methods for targeted delivery, repair, or increased expression of the survival motor neuron protein, SMN. The clinical community is actively collaborating to identify, develop, and validate outcome measures and biomarkers in parallel with laboratory efforts. Innovative trial design and synergistic approaches to maximize proactive care in conjunction with treatment with one or more of the promising pharmacologic and biologic therapies currently in the pipeline will maximize our chances to achieve meaningful outcomes for patients. This review highlights recent promising scientific and clinical advances bringing us ever closer to effective treatment(s) for our patients with SMA.

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“…However, these authors did not detect significant differences between diaphragm and intercostal muscles and also did not report any changes in PSCs. In any case, these early changes do not seem to affect muscle function in the womb, as an ultrasound study did not detect differences in movement between SMA and control foetuses in vivo . There is unfortunately no information whether or how such histopathological changes develop during the remaining two‐thirds of gestation.…”

Section: Discussionmentioning

confidence: 96%