scholarly journals Cervical rotation, chest deformity and pelvic obliquity in patients with spinal muscular atrophy

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Agnieszka Stępień ◽  
Łucja Mazurkiewicz ◽  
Katarzyna Maślanko ◽  
Witold Rekowski ◽  
Maria Jędrzejowska
Keyword(s):  
Spinal Muscular Atrophy ◽  
Cobb Angle ◽  
Musculoskeletal Disorders ◽  
Muscular Atrophy ◽  
Pelvic Obliquity ◽  
Radiographic Evaluation ◽  
Control Group ◽  
Healthy Individuals ◽  
Chest Deformity ◽  
Cervical Rotation

Abstract Background Musculoskeletal disorders are often observed in patients with spinal muscular atrophy (SMA). The aim of the study was to assess passive ranges of rotation in the cervical spine, chest deformity and pelvic obliquity in SMA patients, and to compare these results to the norms obtained in the group of healthy individuals. The second aim was to review these measurements and Cobb angle values for correlations in SMA patients. Methods The study included 74 patients with SMA and 89 healthy individuals aged 2 to 18 years. Cervical Rotation (CR), Supine Angle of Trunk Rotation (SATR) and Pelvic Obliquity (PO) tests were carried out. Results Cervical rotation ranges were significantly higher in the control group than in SMA patients (p < 0.05). Differences between cervical rotation ranges to the left and to the right were significantly larger in SMA I and SMA II groups than in healthy individuals (p = 0.000). Chest asymmetry and pelvic obliquity were bigger in SMA groups than in the control (p < 0.05). Significant correlations between cervical rotation measurements, chest deformity, pelvic obliquity and Cobb angle were found in SMA individuals, depending on the type. Conclusions The results of the study suggest that CR, SATR and PO tests may assist in the assessment of SMA patients in addition to the radiographic evaluation of the spine. Biomechanical relationships between disorders located in various skeletal structures should be taken into account in the treatment of SMA patients. Special attention should be given to assessing postural parameters in non- sitters and sitters. Treatment of patients with SMA and associated musculoskeletal disorders requires a multi-specialist approach.

Children With Spinal Muscular Atrophy With Prior Growth-Friendly Spinal Implants Have Better Results After Definite Spinal Fusion in Comparison to Untreated Patients

Neurosurgery ◽  
2020 ◽  
Vol 87 (5) ◽  
pp. 910-917 ◽  
Author(s):  
Anna K Hell ◽  
Lena Braunschweig ◽  
Konstantinos Tsaknakis ◽  
Urs von Deimling ◽  
Katja A Lüders ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Spinal Muscular Atrophy ◽  
Spinal Fusion ◽  
Muscular Atrophy ◽  
Pelvic Obliquity ◽  
Prior Treatment ◽  
Childhood And Adolescence ◽  
Scoliotic Curve ◽  
Spinal Implants ◽  
Dorsal Spondylodesis

Abstract BACKGROUND Almost all children with spinal muscular atrophy (SMA) develop a scoliosis during childhood and adolescence. In the last decades, growth-friendly spinal implants have been established as an interim solution for these patients until definite spinal fusion can be performed. The effect of those implants on the final outcome has yet to be described. OBJECTIVE To assess the effect of prior growth-friendly spinal surgical treatment on the outcome after spinal fusion in SMA children in comparison to untreated SMA patients through the prospective study. METHODS A total of 28 SMA patients with (n = 14) and without (n = 14) prior surgical treatment with growth-friendly implants were included. Average surgical treatment prior to definite spinal fusion was 4.9 yr. Scoliotic curve angle, pelvic obliquity, spinal length, kyphosis, and lordosis were evaluated for children with prior treatment and before and after dorsal spondylodesis for all children. RESULTS The curve angle before definite spinal fusion averaged at 104° for SMA patients without prior treatment and 71° for patients with prior treatment. Spondylodesis reduced the scoliotic curve to 50° and 33°, respectively, which equals a correction of 52% vs 54%. Pelvic obliquity could be improved by spinal fusion in all patients with better results in the pretreated group. Results for spinal length, kyphosis, and lordosis were similar in both groups. CONCLUSION These data show the positive effect of prior growth-friendly surgical treatment on radiographic results of spinal fusion in children with SMA. Both scoliotic curve angles and pelvic obliquity showed significantly better values when patients had growth-friendly implants before definite spinal fusion.

scholarly journals High-throughput screening reveals novel mutations in spinal muscular atrophy patients

2019 ◽  
Author(s):  
Jianbo Shu ◽  
Jingrui Wang ◽  
Yulian Fang ◽  
Zanmei Xu ◽  
Xiaowei Wang ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
High Throughput ◽  
High Throughput Screening ◽  
High Throughput Sequencing ◽  
Muscular Atrophy ◽  
Point Mutations ◽  
Control Group ◽  
Compound Heterozygous ◽  
Single Nucleotide Variants ◽  
Illumina Hiseq

Abstract Background Some spinal muscular atrophy (SMA) cases are caused by either compound heterozygosity with a point mutation in one allele and a deletion in the other or compound heterozygous point mutations in SMN1 or other genes. Methods To explore more genes and mutations in the onset of SMA, 83 whole blood samples were collected from 28 core families of clinically suspected SMA, and multiplex ligation probe amplification (MLPA) was firstly performed with a SALSA MLPA Kit P021 for preliminary diagnosis. Afterwards, the complete gene sequence of SMN1 gene was detected with the high-throughput sequencing platform of Illumina HiSeq-2500 to find more mutations in the 28 core families. Furthermore, 20 SMA patients were selected from the 28 prodands, and 5 non SMA children as controls. The Life Technologies SOLiD™ technology with mate-pair chemistry was utilized to conduct the whole exome high-throughput sequencing. Results MLPA results showed that 22 probands were SMA patients, 3 probands carriers, and 3 probands normal individuals. Moreover, 2 parents from 2 SMA families were with 3 SMN1 exon7 copies. 6 SMN1 single nucleotide variants (SNVs) were identified in the 83 samples, and c.[84C>T], c.[271C>T], c.[-39A>G] and g.[70240639G>C] were novel. Compared with control group, 9102 mutation were selected out in SMA patients. SPTA1 mutation c.[-41_-40insCTCT], FUT5 SNV c.[1001A>G], and MCCC2 SNV c.[-117A>G] were the 3 most frequent mutations in SMA group (95%, 85% and 75%, respectively). Conclusions We identified some mutations in both SMN1 and other genes, and c.[271C>T], c.[-41_-40insCTCT], c.[1001A>G] and c.[-117A>G] might be associated with the onset of SMA.

scholarly journals Combination Therapy with Nusinersen and Onasemnogene Abeparvovec-xioi in Spinal Muscular Atrophy Type I

2021 ◽  
Vol 10 (23) ◽  
pp. 5540
Author(s):  
Andrada Mirea ◽  
Elena-Silvia Shelby ◽  
Mihaela Axente ◽  
Mihaela Badina ◽  
Liliana Padure ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Spinal Muscular Atrophy ◽  
Motor Function ◽  
Muscular Atrophy ◽  
Combined Therapy ◽  
Genetic Defect ◽  
Survival Motor Neuron ◽  
Control Group ◽  
Type I ◽  
Spinal Muscular Atrophy Type

Background: Spinal muscular atrophy (SMA) is a neuromuscular progressive disease, characterized by decreased amounts of survival motor neuron (SMN) protein, due to an autosomal recessive genetic defect. Despite recent research, there is still no cure. Nusinersen, an antisense oligonucleotide acting on the SMN2 gene, is intrathecally administered all life long, while onasemnogene abeparvovec-xioi, a gene therapy, is administered intravenously only once. Both therapies have proven efficacy, with best outcomes obtained when administered presymptomatically. In recent years, disease-modifying therapies such as nusinersen and onasemnogene abeparvovec-xioi have changed the natural history of SMA. Methods: We observed seven SMA type I patients, who received both therapies. We compared their motor function trajectories, ventilation hours and cough assist sessions to a control group of patients who received one therapy, in order to investigate whether combination therapy may be more effective than a single intervention alone. Results: Patients who received both therapies, compared to the monotherapy cohort, had the same motor function trajectory. Moreover, it was observed that the evolution of motor function was better in the 6 months following the first therapy than in the first 6 months after adding the second treatment. Conclusions: Our results suggest that early treatment is more important than combined therapy.

Electrocardiographic Evaluation in Patients With Spinal Muscular Atrophy: A Case-Control Study

2018 ◽  
Vol 33 (7) ◽  
pp. 487-492 ◽  
Author(s):  
Raffaele Falsaperla ◽  
Giovanna Vitaliti ◽  
Ausilia Desiree Collotta ◽  
Chiara Fiorillo ◽  
Alfredo Pulvirenti ◽  
...  
Keyword(s):  
Heart Rate ◽  
Spinal Muscular Atrophy ◽  
Cardiac Tissue ◽  
Muscular Atrophy ◽  
P Wave ◽  
Cardiac Conduction ◽  
Control Group ◽  
Qrs Complex ◽  
P Waves ◽  
Spinal Muscular Atrophy Type

Background: This study aimed to show the impairment of autonomic cardiac conduction causing bradycardia and/or electrocardiographic alterations in children affected by spinal muscular atrophy type 1 and 2 (SMA 1 and 2). Methods: We included 25 spinal muscular atrophy patients, admitted from November 2016 to May 2017. All patients underwent an electrocardiographic examination and we studied PR and QRS intervals, P-waves and QRS amplitudes, and heart rate in spinal muscular atrophy patients compared to a control group. Results: In all patients, we found longer PRi and QRSi ( P < .05), lower P-wave and QRS complex amplitudes ( P < .01), and a decreased heart rate ( P < .01) with respect to controls. When we divided our patients into SMA1 and SMA2 subgroups, we found that statistical differences were maintained for P-wave and QRS complex amplitudes and heart rate, but not for PRi and QRSi with respect to controls. Conclusion: We suggest the hypothesis of SMN expression on cardiac tissue condition and/or autonomic cardiac conduction.

scholarly journals High-throughput screening reveals novel mutations in spinal muscular atrophy patients

2020 ◽  
Vol 46 (1) ◽  
Author(s):  
Ruiping Zhang ◽  
Chunyu Gu ◽  
Linjie Pu ◽  
Yingtao Meng ◽  
Jianbo Shu ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
High Throughput ◽  
High Throughput Screening ◽  
High Throughput Sequencing ◽  
Muscular Atrophy ◽  
Hereditary Disease ◽  
Control Group ◽  
Single Nucleotide Variants ◽  
Frequent Mutations ◽  
Multiplex Ligation Probe Amplification

Abstract Background Spinal muscular atrophy (SMA) is an autosomal recessive hereditary disease associated with severe muscle atrophy and weakness in the limbs and trunk. The discovery of mutated genes is helpful in diagnosis and treatment for SMA. Methods Eighty-three whole blood samples were collected from 28 core families of clinically suspected SMA, and multiplex ligation probe amplification (MLPA) was performed. Afterwards, the complete gene sequence of SMN1 gene was detected. Furthermore, 20 SMA patients were selected from the 28 probands, and 5 non SMA children as controls. The Life Technologies SOLiD™ technology with mate-pair chemistry was utilized to conduct the whole exome high-throughput sequencing. Results Twenty-two probands were SMA patients, 3 probands carriers, and 3 probands normal individuals. Moreover, 2 parents from 2 SMA families were with 3 SMN1 exon7 copies. Six SMN1 single nucleotide variants (SNVs) were identified in the 83 samples, and c.[84C > T], c.[271C > T], c.[−39A > G] and g.[70240639G > C] were novel. Compared with control group, 9102 mutation were selected out in SMA patients. SPTA1 mutation c.[−41_-40insCTCT], FUT5 SNV c.[1001A > G], and MCCC2 SNV c.[−117A > G] were the 3 most frequent mutations in SMA group (95, 85 and 75%, respectively). Conclusions We identified some mutations in both SMN1 and other genes, and c.[271C > T], c.[−41_-40insCTCT], c.[1001A > G] and c.[−117A > G] might be associated with the onset of SMA.

scholarly journals Hip abduction and supported standing affect the ranges of hips extension in spinal muscular atrophy patients

2020 ◽  
Author(s):  
Agnieszka Stępień ◽  
Joanna Sikora-Chojak ◽  
Katarzyna Maślanko ◽  
Wojciech Kiebzak
Keyword(s):  
Spinal Muscular Atrophy ◽  
Hip Joint ◽  
Sagittal Plane ◽  
Muscular Atrophy ◽  
Lower Limbs ◽  
Control Group ◽  
Hip Joints ◽  
Hip Abduction ◽  
And Control ◽  
Healthy Participants

Introduction: Recommendations for management of spinal muscular atrophy (SMA) do not contain detailed information about the position of lower limbs during support standing. It has been observed that during the measurement of the range of extension in the hip joint (HE) in SMA patients, the examined limb was often naturally abducted. Aim: The main aim of the study was to compare the values of HE in the sagittal plane and in abduction, and to assess the correlation between the duration of supported standing and HE in SMA patients. Material and methods: The study group consisted of 75 SMA individuals aged 2–22 years and control group consisted of 202 healthy participants. The measurements were performed with the Rippstein plurimeter and goniometer. Results and discussion: Range of HE in SMA patients was larger in abduction than in the sagittal plane. A correlation was noted between the duration of supported standing and HE. Conclusions: Supported standing with hip joint abduction should be used in SMA patients. The obtained results broaden the knowledge about the biomechanics of hip joints in SMA patients.

Real-World Data from Nusinersen Treatment for Patients with Later-Onset Spinal Muscular Atrophy: A Single Center Experience

2021 ◽  
Vol 8 (1) ◽  
pp. 101-108
Author(s):  
Rodrigo H. Mendonça ◽  
Graziela J. Polido ◽  
Ciro Matsui ◽  
André M.S. Silva ◽  
Davi J.F. Solla ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Disease Duration ◽  
Muscular Atrophy ◽  
Response To Treatment ◽  
Functional Improvement ◽  
Control Group ◽  
Single Center ◽  
Real World Data

Background Spinal muscular atrophy (SMA) is a motor neuron disease associated with progressive muscle weakness and motor disability. Objective This study aims to report the evaluation of nusinersen, an antisense oligonucleotide, on motor function in patients with SMA types 2 and 3. Methods This single-center retrospective observational study assessed nusinersen therapy outcomes, measured by HSMFSE or CHOP-INTEND scales, in patients with SMA types 2 and 3, compared to untreated patients, for at least 24 months. Results A total of 41 patients with SMA types 2 and 3 under nusinersen treatment were included. In 30 treated patients (mean age: 10.6 years; 14 with SMA type 2), the mean change in HFMSE scores was +1.47 points (SD = 0.4) and +1.60 points (SD = 0.6) after 12 and 24 months of treatment, respectively. In contrast, the control group (N = 37) (mean age: 10.2 years; 20 with SMA type 2) presented a mean change of −1.71 points (SD = 0.02) and −3.93 points (SD = 0.55) after 12 and 24 months of follow-up, respectively. The most severe patients under nusinersen treatment (N = 11) showed a change of +2.37 (SD = 1.13) on the CHOP-INTEND scale after 12 months of follow-up. Disease duration at the beginning of treatment was the main predictor of functional improvement. Despite functional gain and motor stabilization, treatment with nusinersen did not prevent the progression of scoliosis. Conclusions Our data provide evidence for the long-term safety and efficacy of nusinersen use in the treatment of later-onset SMA, and patients with shorter disease duration showed better response to treatment.

scholarly journals High-throughput screening reveals novel mutations in spinal muscular atrophy patients

2020 ◽  
Author(s):  
Ruiping Zhang ◽  
Chunyu Gu ◽  
Linjie Pu ◽  
Yingtao Meng ◽  
Jianbo Shu ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
High Throughput ◽  
High Throughput Screening ◽  
High Throughput Sequencing ◽  
Muscular Atrophy ◽  
Hereditary Disease ◽  
Control Group ◽  
Single Nucleotide Variants ◽  
Frequent Mutations ◽  
Multiplex Ligation Probe Amplification

Abstract Background Spinal muscular atrophy (SMA) is an autosomal recessive hereditary disease associated with severe muscle atrophy and weakness in the limbs and trunk. The discovery of genes mutated by SMA is helpful in diagnosis and treatment. Methods 83 whole blood samples were collected from 28 core families of clinically suspected SMA, and multiplex ligation probe amplification (MLPA) was firstly performed. Afterwards, the complete gene sequence of SMN1 gene was detected. Furthermore, 20 SMA patients were selected from the 28 probands, and 5 non SMA children as controls. The Life Technologies SOLiD™ technology with mate-pair chemistry was utilized to conduct the whole exome high-throughput sequencing. Results 22 probands were SMA patients, 3 probands carriers, and 3 probands normal individuals. Moreover, 2 parents from 2 SMA families were with 3 SMN1 exon7 copies. 6 SMN1 single nucleotide variants (SNVs) were identified in the 83 samples, and c.[84C>T], c.[271C>T], c.[-39A>G] and g.[70240639G>C] were novel. Compared with control group, 9102 mutation were selected out in SMA patients. SPTA1 mutation c.[-41_-40insCTCT], FUT5 SNV c.[1001A>G], and MCCC2 SNV c.[-117A>G] were the 3 most frequent mutations in SMA group (95%, 85% and 75%, respectively). Conclusions We identified some mutations in both SMN1 and other genes, and c.[271C>T], c.[-41_-40insCTCT], c.[1001A>G] and c.[-117A>G] might be associated with the onset of SMA.

scholarly journals High-throughput screening reveals novel mutations in spinal muscular atrophy patients

2020 ◽  
Author(s):  
Ruiping Zhang ◽  
Chunyu Gu ◽  
Linjie Pu ◽  
Yingtao Meng ◽  
Jianbo Shu ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
High Throughput ◽  
High Throughput Screening ◽  
High Throughput Sequencing ◽  
Muscular Atrophy ◽  
Hereditary Disease ◽  
Control Group ◽  
Single Nucleotide Variants ◽  
Frequent Mutations ◽  
Multiplex Ligation Probe Amplification

Abstract Background: Spinal muscular atrophy (SMA) is an autosomal recessive hereditary disease associated with severe muscle atrophy and weakness in the limbs and trunk. The discovery of mutated genes is helpful in diagnosis and treatment for SMA. Methods: 83 whole blood samples were collected from 28 core families of clinically suspected SMA, and multiplex ligation probe amplification (MLPA) was performed. Afterwards, the complete gene sequence of SMN1 gene was detected. Furthermore, 20 SMA patients were selected from the 28 probands, and 5 non SMA children as controls. The Life Technologies SOLiD™ technology with mate-pair chemistry was utilized to conduct the whole exome high-throughput sequencing. Results: 22 probands were SMA patients, 3 probands carriers, and 3 probands normal individuals. Moreover, 2 parents from 2 SMA families were with 3 SMN1 exon7 copies. 6 SMN1 single nucleotide variants (SNVs) were identified in the 83 samples, and c.[84C>T], c.[271C>T], c.[-39A>G] and g.[70240639G>C] were novel. Compared with control group, 9102 mutation were selected out in SMA patients. SPTA1 mutation c.[-41_-40insCTCT], FUT5 SNV c.[1001A>G], and MCCC2 SNV c.[-117A>G] were the 3 most frequent mutations in SMA group (95%, 85% and 75%, respectively). Conclusions: We identified some mutations in both SMN1 and other genes, and c.[271C>T], c.[-41_-40insCTCT], c.[1001A>G] and c.[-117A>G] might be associated with the onset of SMA.

scholarly journals Continuous lengthening potential after four years of magnetically controlled spinal deformity correction in children with spinal muscular atrophy

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Heiko M. Lorenz ◽  
Marina M. Hecker ◽  
Lena Braunschweig ◽  
Batoul Badwan ◽  
Konstantinos Tsaknakis ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Spinal Deformity ◽  
Muscular Atrophy ◽  
Deformity Correction ◽  
Pelvic Obliquity ◽  
Complication Rates ◽  
Scoliotic Curve ◽  
Level Of Evidence ◽  
Growing Rods

AbstractMagnetically controlled growing rods (MCGR) are commonly implanted for the treatment of early-onset scoliosis. While most authors report favorable short-term results, little is known about long-term deformity correction. This prospective cohort study assesses spinal deformity control in a homogeneous spinal muscular atrophy (SMA) patient group treated with MCGR implants, a standardized lengthening protocol and a minimum follow-up of four years. 17 SMA patients with progressive scoliosis were treated with MCGR implanted parallel to the spine with rib-to-pelvis fixation. Radiologic measurements were performed before and after MCGR implantation and during external lengthening procedures. These included measurements of the scoliotic curve, kyphosis, lordosis, pelvic obliquity and the spinal length. Additional clinical data of the complications were also analyzed. 17 children (mean age 7.4 years) were surgically treated and underwent a total of 376 lengthenings. Complication rates were 3.5% in respect to all interventions or 41% of the patients had complications during 3.5% of the lengthening sessions. The initial implantation significantly reduced the main scoliotic curve by 59%, with the correction remaining constant throughout the follow-up. Pelvic obliquity was also significantly and permanently corrected by 72%, whereas kyphosis and lordosis were not influenced. The spinal length could be significantly increased mostly during the first year of treatment. Bilateral implantation of MCGRs for correction of spinal deformity in children with SMA showed no decrease of the lengthening potential during a four-year follow-up. Therefore, the previously described ‘law of diminishing returns’ could not be applied to this patient population.Level of Evidence/Clinical relevance: Therapeutic Level IV.

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