Growth patterns in children with spinal muscular atrophy

Abstract Background Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by muscle atrophy and weakness. SMA type 1 (SMA1) is the most severe form: affected infants are unable to sit unaided; SMA type 2 (SMA2) children can sit, but are not able to walk independently. The Standards of Care has improved quality of life and the increasing availability of disease-modifying treatments is progressively changing the natural history; so, the clinical assessment of nutritional status has become even more crucial. Aims of this multicenter study were to present the growth pattern of treatment-naïve SMA1 and SMA2, and to compare it with the general growth standards. Results Body Weight (BW, kg) and Supine Length (SL, cm) were collected using a published standardized procedure. SMA-specific growth percentiles curves were developed and compared to the WHO reference data. We recruited 133 SMA1 and 82 SMA2 (48.8% females). Mean ages were 0.6 (0.4–1.6) and 4.1 (2.1–6.7) years, respectively. We present here a set of disease-specific percentiles curves of BW, SL, and BMI-for-age for girls and boys with SMA1 and SMA2. These curves show that BW is significantly lower in SMA than healthy peers, while SL is more variable. BMI is also typically lower in both sexes and at all ages. Conclusions These data on treatment-naïve patients point toward a better understanding of growth in SMA and could be useful to improve the clinical management and to assess the efficacy of the available and forthcoming therapies not only on motor function, but also on growth.

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Tracheotomy and children with spinal muscular atrophy type 1

Nursing Ethics ◽

10.1177/0969733011429014 ◽

2012 ◽

Vol 19 (3) ◽

pp. 408-418 ◽

Cited By ~ 14

Author(s):

Brigitte Rul ◽

Franco Carnevale ◽

Brigitte Estournet ◽

Michèle Rudler ◽

Christian Hervé

Keyword(s):

Mechanical Ventilation ◽

Spinal Muscular Atrophy ◽

Motor Neurons ◽

Muscular Atrophy ◽

Severe Form ◽

First Year ◽

Spinal Muscular Atrophy Type ◽

Intellectual Capacity ◽

First Year Of Life

Spinal muscular atrophy (SMA) type 1 is a genetic neuromuscular disease in children that leads to degeneration of spinal cord motor neurons. This sometimes results in severe muscular paralysis requiring mechanical ventilation to sustain the child’s life. The onset of SMA type 1, the most severe form of the disease, is during the first year of life. These children become severely paralysed, but retain their intellectual capacity. Ethical concerns arise when mechanical ventilation becomes necessary for survival. When professionals assess the resulting life for the child and family, they sometimes fear it will result in unreasonably excessive care. The aim of this article is to present an analysis of ethical arguments that could support or oppose the provision of invasive ventilation in this population. This examination is particularly relevant as France is one of the few countries performing tracheotomies and mechanical ventilation for this condition.

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Gene therapy for spinal muscular atrophy: the Qatari experience

Gene Therapy ◽

10.1038/s41434-021-00273-7 ◽

2021 ◽

Author(s):

Hossamaldein Gaber Ali ◽

Khalid Ibrahim ◽

Mahmoud Fawzi Elsaid ◽

Reem Babiker Mohamed ◽

Mahmoud I. A. Abeidah ◽

...

Keyword(s):

Gene Therapy ◽

Spinal Muscular Atrophy ◽

Troponin I ◽

Muscular Atrophy ◽

Neuromuscular Disorders ◽

Neuromuscular Disorder ◽

Progressive Muscle Weakness ◽

Elevated Bilirubin

AbstractSpinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by hypotonia, progressive muscle weakness, and wasting. Onasemnogene abeparvovec (Zolgensma®) is a novel gene therapy medicine, FDA-approved in May 2019 for the treatment of SMA. This study aimed to describe Qatari experience with onasemnogene abeparvovec by reviewing the clinical outcomes of 9 SMA children (7 SMA type 1 and 2 with SMA type 2) aged 4‒23 months treated between November 2019 and July 2020. Children <2 years with 5q SMA with a bi-allelic mutation in the SMN1 gene were eligible for gene therapy. Liver function (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and total bilirubin), platelet count, coagulation profile, troponin-I levels, and motor scores (Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders [CHOP INTEND]), were regularly monitored following gene therapy. All patients experienced elevated AST or ALT, two experienced high prothrombin time, and one experienced elevated bilirubin; all of these patients were asymptomatic. Furthermore, one event of vomiting after infusion was reported in one patient. Significant improvements in CHOP INTEND scores were observed following therapy. This study describes the short-term outcomes and safety of onasemnogene abeparvovec, which is well tolerated and shows promise for early efficacy.

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Distal Spinal Muscular Atrophy: An Overlooked Etiology of Weaning Failure in Children with Respiratory Insufficiency

Journal of Pediatric Intensive Care ◽

10.1055/s-0037-1617434 ◽

2018 ◽

Vol 07 (03) ◽

pp. 159-162 ◽

Cited By ~ 1

Author(s):

Asgar Eghbalkhah ◽

Kamyar Kamrani ◽

Nahid Khosroshahi ◽

Hossein Yousefimanesh ◽

Zahra Eskandarizadeh ◽

...

Keyword(s):

Respiratory Distress ◽

Spinal Muscular Atrophy ◽

Motor Neurons ◽

Respiratory Insufficiency ◽

Muscular Atrophy ◽

Pediatric Intensive Care ◽

Neuromuscular Disorder ◽

Weaning Failure ◽

Life Threatening

AbstractSpinal muscular atrophy with respiratory distress type 1 (SMARD1) is a rare autosomal recessive neuromuscular disorder that involves the anterior horn motor neurons. It is a disease with a poor prognosis presenting with progressive distal motor weakness and respiratory insufficiency from diaphragmatic paralysis followed by distal muscle weakness before 6 months of age. With the intent to spread the awareness of this rare and life-threatening disease, we report a 2.5-month-old female infant with a subsequent diagnosis of SMARD1, who was admitted in our pediatric intensive care unit with chief complaint of progressive respiratory distress and poor feeding.

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Cervical puncture to deliver nusinersen in patients with spinal muscular atrophy

Neurology ◽

10.1212/wnl.0000000000006006 ◽

2018 ◽

Vol 91 (7) ◽

pp. e620-e624 ◽

Cited By ~ 13

Author(s):

Aravindhan Veerapandiyan ◽

Ria Pal ◽

Stephen D'Ambrosio ◽

Iris Young ◽

Katy Eichinger ◽

...

Keyword(s):

Spinal Muscular Atrophy ◽

Spinal Fusion ◽

Tissue Concentration ◽

Muscular Atrophy ◽

Retrospective Chart Review ◽

Neuromuscular Disorder ◽

Spinal Cord Tissue ◽

Posterior Aspect ◽

Feasible Alternative

ObjectiveTo report our experience delivering intrathecal nusinersen through cervical puncture in patients with spinal muscular atrophy (SMA) with no lumbar access.BackgroundSMA is a neuromuscular disorder characterized by profound muscle weakness, atrophy, and paralysis due to degeneration of the anterior horn cells. Nusinersen, the first Food and Drug Administration–approved treatment for SMA, is administered intrathecally via lumbar puncture; however, many patients with SMA have scoliosis or solid spinal fusion with hardware that makes lumbar access impossible. Studies in primates have demonstrated better spinal cord tissue concentration with intrathecal injections than with intracerebral ventricular injections. Therefore we have used C1/C2 puncture as an alternative to administer nusinersen.MethodRetrospective chart review.ResultsIntrathecal nusinersen via cervical puncture was given to 3 patients who had thoracic and lumbosacral spinal fusion: a 12-year-old girl with type 1 SMA and 2 17-year-old girls with type 2 SMA. Cervical puncture was performed without deep sedation under fluoroscopic guidance using a 25-G or a 24-G Whitacre needle in the posterior aspect of C1-C2 interspace and full dose of nusinersen (12 mg/5 mL) was injected after visualizing free CSF flow. Patients completed their 4 loading doses and first maintenance dose of nusinersen, and 15 procedures were successful and well-tolerated.ConclusionCervical puncture is a feasible alternative delivery route to administer intrathecal nusinersen in patients with longstanding SMA and spine anatomy precluding lumbar access when done by providers with expertise in this procedure.

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Observations from a nationwide vigilance program in medical care for spinal muscular atrophy patients in Chile

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20190073 ◽

2019 ◽

Vol 77 (7) ◽

pp. 470-477

Author(s):

Karin ALVAREZ ◽

Bernardita SUAREZ ◽

María Angélica PALOMINO ◽

Cecilia HERVIAS ◽

Giancarlo CALCAGNO ◽

...

Keyword(s):

Spinal Muscular Atrophy ◽

Copy Number ◽

Muscular Atrophy ◽

Genetic Diagnosis ◽

Standards Of Care ◽

Scoliosis Surgery ◽

Timely Access ◽

Type 3

ABSTRACT Spinal muscular atrophy (SMA) has gained much attention in the last few years because of the approval of the first intrathecal treatment for this neurodegenerative disease. Latin America needs to develop the demographics of SMA, timely access to diagnosis, and appropriate following of the standards of care recommendations for patients. These are essential steps to guide health policies. Methods This was a descriptive study of a cohort of SMA patients from all over Chile. We analyzed the clinical, motor functional, and social data, as well as the care status of nutritional, respiratory and skeletal conditions. We also measured the SMN2 copy number in this population. Results We recruited 92 patients: 50 male; 23 SMA type-1, 36 SMA type-2 and 33 SMA type-3. The median age at genetic diagnosis was 5, 24 and 132 months. We evaluated the SMN2 copy number in 57 patients. The SMA type-1 patients were tracheostomized and fed by gastrostomy in a 69.6 % of cases, 65% of SMA type-2 patients received nocturnal noninvasive ventilation, and 37% of the whole cohort underwent scoliosis surgery. Conclusion Ventilatory care for SMA type-1 is still based mainly on tracheostomy. This Chilean cohort of SMA patients had timely access to genetic diagnosis, ventilatory assistance, nutritional support, and scoliosis surgery. In this series, SMA type-1 is underrepresented, probably due to restrictions in access to early diagnosis and the high and early mortality rate.

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Spinal Muscular Atrophy Type 1 Quality of Life

American Journal of Physical Medicine & Rehabilitation ◽

10.1097/00002060-200302000-00009 ◽

2003 ◽

Vol 82 (2) ◽

pp. 137-142 ◽

Cited By ~ 65

Author(s):

John R. Bach ◽

Jose Vega ◽

Jennifer Majors ◽

Al Friedman

Keyword(s):

Quality Of Life ◽

Spinal Muscular Atrophy ◽

Muscular Atrophy ◽

Spinal Muscular Atrophy Type

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Nutritional, Gastrointestinal and Endo-Metabolic Challenges in the Management of Children with Spinal Muscular Atrophy Type 1

Nutrients ◽

10.3390/nu13072400 ◽

2021 ◽

Vol 13 (7) ◽

pp. 2400

Author(s):

Antonio Corsello ◽

Lorenzo Scatigno ◽

Martina Chiara Pascuzzi ◽

Valeria Calcaterra ◽

Dario Dilillo ◽

...

Keyword(s):

Spinal Muscular Atrophy ◽

Muscular Atrophy ◽

Clinical Care ◽

Palliative Therapy ◽

Childhood And Adolescence ◽

Spinal Muscular Atrophy Type ◽

History Of ◽

Insight Into

The management of patients with spinal muscular atrophy type 1 (SMA1) is constantly evolving. In just a few decades, the medical approach has switched from an exclusively palliative therapy to a targeted therapy, transforming the natural history of the disease, improving survival time and quality of life and creating new challenges and goals. Many nutritional problems, gastrointestinal disorders and metabolic and endocrine alterations are commonly identified in patients affected by SMA1 during childhood and adolescence. For this reason, a proper pediatric multidisciplinary approach is then required in the clinical care of these patients, with a specific focus on the prevention of most common complications. The purpose of this narrative review is to provide the clinician with a practical and usable tool about SMA1 patients care, through a comprehensive insight into the nutritional, gastroenterological, metabolic and endocrine management of SMA1. Considering the possible horizons opened thanks to new therapeutic frontiers, a nutritional and endo-metabolic surveillance is a crucial element to be considered for a proper clinical care of these patients.

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Treatment with nusinersen in a girl with spinal muscular atrophy type 1 - Case report

Slovenian Medical Journal ◽

10.6016/zdravvestn.2902 ◽

2020 ◽

Vol 89 (5-6) ◽

pp. 320-326

Author(s):

Tanja Loboda ◽

Tita Butenko ◽

Tanja Golli ◽

Damjan Osredkar

Keyword(s):

Spinal Muscular Atrophy ◽

Respiratory Infections ◽

Muscular Atrophy ◽

Neuromuscular Disorders ◽

Neuromuscular Disorder ◽

Natural Course ◽

Dramatic Improvement ◽

Serious Adverse Events ◽

Spinal Muscular Atrophy Type

We report the case of a girl with spinal muscular atrophy (SMA) type 1, who is the first patient with SMA in Slovenia treated with nusinersen, the first disease modifying therapy available for these patients. SMA is an autosomal recessive neuromuscular disorder characterized by muscle weakness, atrophy and paralysis due to the degeneration of the anterior horn cells, leading to premature death, most commonly due to respiratory infections. Nusinersen, an antisense oligonucleotide, was clinically approved based on clinical trials showing dramatic improvement in the natural course of infantile-onset SMA. After the genetic confirmation of SMA, our girl was the first child in Slovenia to receive nusinersen, which was provided through an expanded access programme. She received intrathecal applications of nusinersen according to the protocol. No serious adverse events were observed. Assessment of her motor skills was performed using The Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP – INTEND) before the beginning of treatment and after completing the first 7 applications of nusinersen. She scored 21/64 points before the introduction of treatment and 32/64 after the completion of treatment. In conclusion, nusinersen improved the CHOP – INTEND motor function score and has been effective in delaying the expected natural course of SMA in our patient.

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Nutritional, Gastrointestinal and Endo-Metabolic Traps in the Management of Children with Spinal Muscular Atrophy Type 1

10.20944/preprints202106.0184.v1 ◽

2021 ◽

Author(s):

Antonio Corsello ◽

Lorenzo Scatigno ◽

Martina Chiara Pascuzzi ◽

Valeria Calcaterra ◽

Dario Dilillo ◽

...

Keyword(s):

Spinal Muscular Atrophy ◽

Muscular Atrophy ◽

Clinical Care ◽

Palliative Therapy ◽

Childhood And Adolescence ◽

Spinal Muscular Atrophy Type ◽

History Of ◽

Insight Into

The management of patients with spinal muscular atrophy type 1 (SMA1) is constantly evolving. In just a few decades the medical approach has switched from an exclusively palliative therapy to a targeted therapy, transforming the natural history of the disease, improving survival time and quality of life, and creating new challenges and goals. Many nutritional problems, gastrointesti-nal disorders and metabolic and endocrine alterations are commonly identified in patients af-fected by SMA1 during childhood and adolescence. For this reason, a proper pediatric multidis-ciplinary approach is then required in the clinical care of these patients, with a specific focus on the prevention of most common complications. The purpose of this narrative review is to provide the clinician with a practical and usable tool about SMA1 patients care, through a comprehensive insight into the nutritional, gastroenterological, metabolic and endocrine management of SMA1. Considering the possible horizons opened thanks to new therapeutic frontiers, a nutritional and endo-metabolic surveillance is a crucial element to be considered for a proper clinical care of these patients.

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Cytochemical Characterization of Cerebrospinal Fluid Macrophage Inclusions in Pediatric Patients Receiving Intrathecal Nusinersen (SPINRAZA®) for Spinal Muscular Atrophy

Acta Cytologica ◽

10.1159/000518005 ◽

2021 ◽

pp. 1-6

Author(s):

Kristian T. Schafernak ◽

Jeffrey R. Jacobsen ◽

Dulce Hernandez ◽

Robin D. Kaye ◽

Sylvia E. Perez

Keyword(s):

Cerebrospinal Fluid ◽

Spinal Muscular Atrophy ◽

Pediatric Patients ◽

Muscular Atrophy ◽

Exon Skipping ◽

Neuromuscular Disorder ◽

Case Presentation ◽

Smn Protein

Introduction: Spinal muscular atrophy (SMA) is a debilitating neuromuscular disorder caused by biallelic deletion of the SMN1 gene. Nusinersen, an antisense oligonucleotide delivered intrathecally, binds to the pre-mRNA of SMN1’s pseudogene, SMN2, to prevent exon skipping and produce functional SMN protein to compensate for the deficiency caused by SMN1 deletion. Case Presentation: We reviewed 15 cerebrospinal fluid (CSF) cytology specimens from 8 patients receiving nusinersen for SMA. Macrophages with peculiar inclusions (“nusinophages”) were seen in 8 specimens from 4 of the patients: 1 infant and 3 children with SMA type 1. This finding has only previously been reported in adults with SMA types 2 and 3 and in 2 infants with SMA type 1. Discussion/Conclusion: Specimens containing nusinophages had a significantly higher proportion of macrophages and lower proportion of lymphocytes than those in which nusinophages were not detected. The macrophage inclusions do not represent iron or microorganisms and instead are composed, at least in part, of glycosaminoglycans. Because CSF is a common specimen type, cytotechnologists and cytopathologists need to be aware of these inclusions, so they do not interpret them erroneously as evidence of infection or hemorrhage, especially in light of the fact that oligonucleotide therapy has been approved for a variety of conditions and is currently under investigation for intrathecal delivery in several other neurodegenerative disorders.

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