SMA – OUTCOME MEASURES AND REGISTRIES

peer reviewe

Schizencephaly associated with a severe prothrombotic syndrome caused by antithombin III deficiency

peer reviewedaudience: professional, studen

Application for primary endpoint qualification of the 95th centile of stride velocity (SV95C) in Duchenne muscular dystrophy

peer reviewe

Three years pilot of spinal muscular atrophy newborn screening turned into official program in Southern Belgium.

Three new therapies for spinal muscular atrophy (SMA) have been approved by the United States Food and Drug Administration and the European Medicines Agency since 2016. Although these new therapies improve the quality of life of patients who are symptomatic at first treatment, administration before the onset of symptoms is significantly more effective. As a consequence, newborn screening programs have been initiated in several countries. In 2018, we launched a 3-year pilot program to screen newborns for SMA in the Belgian region of Liège. This program was rapidly expanding to all of Southern Belgium, a region of approximately 55,000 births annually. During the pilot program, 136,339 neonates were tested for deletion of exon 7 of SMN1, the most common cause of SMA. Nine SMA cases with homozygous deletion were identified through this screen. Another patient was identified after presenting with symptoms and was shown to be heterozygous for the SMN1 exon 7 deletion and a point mutation on the opposite allele. These ten patients were treated. The pilot program has now successfully transitioned into the official neonatal screening program in Southern Belgium. The lessons learned during implementation of this pilot program are reported

Leveraging Natural History Data in One- and Two-Arm Hierarchical Bayesian Studies of Rare Disease Progression

peer reviewedThe small sample sizes inherent in rare and pediatric disease settings offer significant challenges for clinical trial design. In such settings, Bayesian adaptive trial methods can often pay dividends, allowing the sensible incorporation of auxiliary data and other relevant information to bolster that collected by the trial itself. Previous work has also included the use of one-arm trials augmented by the participants’ own natural history data, from which the future course of the disease in the absence of intervention can be predicted. Patient response can then be defined by the degree to which post-intervention observations are inconsistent with the predicted “natural” trajectory. While such trials offer obvious advantages in efficiency and ethical hazard (since they expose no new patients to a placebo, anathema to patients or their parents and caregivers), they can offer no protection against bias arising from the presence of any “placebo effect,” the tendency of patients to improve merely by being in the trial. In this paper, we investigate the impact of both static and transient placebo effects on one-arm responder studies of this type, as well as two-arm versions that incorporate a small concurrent placebo group but still borrow strength from the natural history data. We also propose more traditional Bayesian changepoint models that specify a parametric functional form for the patient’s post-intervention trajectory, which in turn allow quantification of the treatment benefit in terms of the model parameters, rather than semi-parametrically in terms of a response relative to some “null” model. We compare the operating characteristics of our designs in the context of an ongoing investigation of centronuclear myopathies (CNMs), a group of congenital neuromuscular diseases whose most common and severe form is X-linked, affecting approximately 1 in 50,000 newborn boys. Our results indicate our two-arm responder and changepoint methods can offer protection against placebo effects, improving power while protecting the trial’s Type I error rate. However, further research into innovative trial designs as well as ongoing dialog with regulatory authorities remain critically important in rare disease research

Early onset dystonia 11

Description d'un cas de dystonie de type 11 (myoclonus-dystonia) à début précoc

A propos d'un cas d'hémiparésie aigue chez l'enfant

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Aspects neurologiques associés au Syndrome de Down

peer reviewedSummary : Down syndrome is one of best caracterized genetic syndromes. Its phenotype includes specific morphological features, mental retardation and several organic impairments such as cardiac malformations, cutaneous disorders and immunologic abnormalities. Beside these disturbances neurological disorders have been less considered or thought to be the expression of the mental retardation. However it is important to pay attention to the high incidence of epilepsy such as West syndrome in infants and “Late-Onset of myoclonic epilepsy in Down Syndrome” in the adult. They might required specific treatment. ADHD as well as autistic behavior may be difficult to diagnose especially in children with severe mental retardation. They need precise attention and rigourous follow-up of their treatment

Infantile spinal muscular atrophy: Therapeutic (R)evolution

Summary: Spinal muscular atrophy (SMA) is an auto-somal recessive neuromuscular disorder. The infantile form is the most common genetic cause of infantile death due to respiratory insufficiency. The disorder is caused by the premature death of motor neurons of anterior horn, leading to progressive weakness and muscular atrophy. Longtime considered as untreatable, the pathology knew a real revolution during the last two years. Views on this terrible disease have completely changed, changing, therefore, the management of the patients and constituting new challenges. © 2019 Revue Medicale de Liege. All Rights Reserved

Juvenil autoimmune myasthenia

peer reviewedWe report the story of an 11-year-old girl admitted to the emergency room for diplopia and divergent squint. Promptly apparead a fluctuating ptosis, a nasal voice and swallowing disorders, evoking the diagnosis of autoimmune myasthenia. The latter has been confirmed with electromyogram. Treatment with corticoids, plasmapheresis and pyridostigmine allowed symptoms control. Thymectomy by left thoracoscopy, non-robot assisted, was performed 6 months after the appearance of the first clinical signs for the purpose of remission