Neuromuscular Disorders and Complications: In the Challenge Lies a Solution

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Clinical Neurology".

Deadline for manuscript submissions: closed (25 February 2024) | Viewed by 23922

Special Issue Editor


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Guest Editor
Pediatric Neurology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
Interests: neuromuscular disorders; spinal muscular atrophy; duchenne muscular dystrophy; child neurology

Special Issue Information

Dear Colleagues,

Advances in technologies, rehabilitation strategies, outcome measures, and biomarker research have enabled the implementation of more efficient ways to implement multidisciplinary approaches to neuromuscular disorders. Furthermore, with new clinical trials and pharmacological treatments being approved, our community is experiencing both exciting times and new challenges.

We are happy to invite you to submit a paper to the Journal of Clinical Medicine for the Special Issue entitles “Neuromuscular Disorders and Complications: In the Challenge Lies a Solution”. This Special Issue aims to showcase the current progress on neuromuscular care with a particular focus on new ways to approach and study old problems. Both research and review papers are welcome for possible publication in this Special Issue.

I hope that your contributions will inspire our readers to explore this field further.

We are looking forward to hearing from you soon.

Kind regards,

Dr. Giorgia Coratti
Guest Editor

Manuscript Submission Information

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Keywords

  • neuromuscular Disorders
  • disease-modifying treatments
  • outcomes of disease progression
  • bulbar function
  • biomarkers
  • respir-atory function
  • artificial intelligence
  • phenotypes

Published Papers (14 papers)

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10 pages, 1278 KiB  
Article
Beyond Contractures in Spinal Muscular Atrophy: Identifying Lower-Limb Joint Hypermobility
by Elizabeth R. Harding, Cara H. Kanner, Amy Pasternak, Allan M. Glanzman, Sally Dunaway Young, Ashwini K. Rao, Michael P. McDermott, Zarazuela Zolkipli-Cunningham, John W. Day, Richard S. Finkel, Basil T. Darras, Darryl C. De Vivo and Jacqueline Montes
J. Clin. Med. 2024, 13(9), 2634; https://doi.org/10.3390/jcm13092634 - 30 Apr 2024
Viewed by 1436
Abstract
Background: The natural history of spinal muscular atrophy (SMA) is well understood, with progressive muscle weakness resulting in declines in function. The development of contractures is common and negatively impacts function. Clinically, joint hypermobility (JH) is observed but is poorly described, and its [...] Read more.
Background: The natural history of spinal muscular atrophy (SMA) is well understood, with progressive muscle weakness resulting in declines in function. The development of contractures is common and negatively impacts function. Clinically, joint hypermobility (JH) is observed but is poorly described, and its relationship with function is unknown. Methods: Lower-limb ROM (range of motion) assessments of extension and flexion at the hip, knee, and ankle were performed. ROMs exceeding the published norms were included in the analysis. The functional assessments performed included the six-minute walk test (6 MWT) and the Hammersmith Functional Motor Scale—Expanded (HFMSE). Results: Of the 143 participants, 86% (n = 123) had at least one ROM measure that was hypermobile, and 22% (n = 32) had three or more. The HFMSE scores were inversely correlated with hip extension JH (r = −0.60, p = 0.21; n = 6) and positively correlated with knee flexion JH (r = 0.24, p = 0.02, n = 89). There was a moderate, inverse relationship between the 6 MWT distance and ankle plantar flexion JH (r = −0.73, p = 0.002; n = 15). Conclusions: JH was identified in nearly all participants in at least one joint in this study. Hip extension, knee flexion and ankle plantar flexion JH was associated with function. A further understanding of the trajectory of lower-limb joint ROM is needed to improve future rehabilitation strategies. Full article
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24 pages, 5157 KiB  
Article
Autoimmune and Non-Autoimmune Comorbidities in Myasthenic Patients of East-European Descent: A Case–Control Study
by Cristina Georgiana Croitoru, Mariana Pavel-Tanasa, Dan Iulian Cuciureanu, Diana Nicoleta Hodorog and Petru Cianga
J. Clin. Med. 2024, 13(8), 2273; https://doi.org/10.3390/jcm13082273 - 14 Apr 2024
Viewed by 660
Abstract
Background: As the life expectancy of patients with myasthenia gravis (MG) is improving, so the number of comorbidities continues to rise, with a potentially significant impact on the overall morbidity and mortality. The main aim of the study was to assess comorbidities of [...] Read more.
Background: As the life expectancy of patients with myasthenia gravis (MG) is improving, so the number of comorbidities continues to rise, with a potentially significant impact on the overall morbidity and mortality. The main aim of the study was to assess comorbidities of MG in a group of patients of East-European descent. Methods: We retrospectively compared 185 adult myasthenic patients with 895 sex- and age-matched controls, admitted from January 2013 to December 2021. Results: Of these patients, 60% had late-onset MG (LOMG), with a clear predominance of women in both the LOMG and early-onset (EOMG) types; and 23.8% of the patients had a radiological description consistent with thymoma. All myasthenic patients had at least one comorbidity; 20 (10.8%) of the patients associated at least one autoimmune comorbidity. Obesity (p < 0.01), type 2 diabetes (p < 0.0001), cerebrovascular diseases (p < 0.0001), essential hypertension (p < 0.01), and cardiac arrythmias (p < 0.0001) were more frequent in patients than in the control group. The granulocyte-to-lymphocyte ratio was higher in the myasthenic patients compared to the controls (p < 0.01 for LOMG). Discussion: We, thus, suggest a common chronic low-grade inflammatory background as a possible connection between MG subtypes and some of these apparently unconnected comorbidities. Conclusions: The East-European origin of the patients offered a different social and cultural angle of a disease studied mainly on populations of West-European and Asian descent. Full article
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14 pages, 4259 KiB  
Article
Evaluation of Neuromuscular Diseases and Complaints by Quantitative Muscle MRI
by Lara Schlaffke, Robert Rehmann, Anne-Katrin Güttsches, Matthias Vorgerd, Christine H. Meyer-Frießem, Hubert R. Dinse, Elena Enax-Krumova, Martijn Froeling and Johannes Forsting
J. Clin. Med. 2024, 13(7), 1958; https://doi.org/10.3390/jcm13071958 - 28 Mar 2024
Viewed by 798
Abstract
Background: Quantitative muscle MRI (qMRI) is a promising tool for evaluating and monitoring neuromuscular disorders (NMD). However, the application of different imaging protocols and processing pipelines restricts comparison between patient cohorts and disorders. In this qMRI study, we aim to compare dystrophic (limb-girdle [...] Read more.
Background: Quantitative muscle MRI (qMRI) is a promising tool for evaluating and monitoring neuromuscular disorders (NMD). However, the application of different imaging protocols and processing pipelines restricts comparison between patient cohorts and disorders. In this qMRI study, we aim to compare dystrophic (limb-girdle muscular dystrophy), inflammatory (inclusion body myositis), and metabolic myopathy (Pompe disease) as well as patients with post-COVID-19 conditions suffering from myalgia to healthy controls. Methods: Ten subjects of each group underwent a 3T lower extremity muscle MRI, including a multi-echo, gradient-echo, Dixon-based sequence, a multi-echo, spin-echo (MESE) T2 mapping sequence, and a spin-echo EPI diffusion-weighted sequence. Furthermore, the following clinical assessments were performed: Quick Motor Function Measure, patient questionnaires for daily life activities, and 6-min walking distance. Results: Different involvement patterns of conspicuous qMRI parameters for different NMDs were observed. qMRI metrics correlated significantly with clinical assessments. Conclusions: qMRI metrics are suitable for evaluating patients with NMD since they show differences in muscular involvement in different NMDs and correlate with clinical assessments. Still, standardisation of acquisition and processing is needed for broad clinical use. Full article
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12 pages, 1852 KiB  
Article
Low Bone Mass in Ambulatory Spinal Muscular Atrophy: A Proactive Approach for an Often-Overlooked Impairment
by Caitlin Trancho, Bailey Stickney, Stacy Kinirons, David Uher, Cara H. Kanner, Ashwini K. Rao, Michael P. McDermott, Carol Ewing Garber, Darryl C. De Vivo and Jacqueline Montes
J. Clin. Med. 2024, 13(5), 1336; https://doi.org/10.3390/jcm13051336 - 27 Feb 2024
Viewed by 991
Abstract
Background: Individuals with spinal muscular atrophy (SMA) are at risk for low bone mass (LBM). The objectives of this study were to compare bone mineral density (BMD) in ambulatory SMA and control participants, identify LBM, and evaluate the associations of function and physical [...] Read more.
Background: Individuals with spinal muscular atrophy (SMA) are at risk for low bone mass (LBM). The objectives of this study were to compare bone mineral density (BMD) in ambulatory SMA and control participants, identify LBM, and evaluate the associations of function and physical activity (PA) with LBM. Methods: Thirty-five children and adults, nineteen SMA and sixteen healthy controls, participated. Dual-energy absorptiometry determined BMD, T-scores, and Z-scores. The six-minute walk test (6MWT) and Timed Up and Go (TUG) assessed function. The International Physical Activity Questionnaire Short Form (IPAQ-SF) evaluated PA. Results: Group comparisons and factors associated with BMD were analyzed. Area under the receiver operating characteristic (ROC) curve (AUC) assessed the ability to identify individuals with LBM. SMA participants had lower BMD (p < 0.001) and increased odds of having LBM relative to controls (OR = 16.7; 95%CI: 1.8–152.8; p = 0.004). Conclusions: Ten SMA and one control had LBM. Z-score was associated with 6MWT (rs = 0.65; p < 0.001) and TUG (rs = −0.61; p < 0.001). IPAQ-SF and Z-score were weakly associated (rs = 0.36, p < 0.03). 6MWT (AUC: 0.80; 95% CI: 0.65–0.94; p = 0.006) and TUG (AUC: 0.85; 95% CI: 0.71–0.98; p = 0.002) identified individuals with LBM. Function, assessed by the 6MWT and TUG, is associated with BMD and shows promise for use in identifying individuals with LBM. Full article
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15 pages, 1385 KiB  
Article
Use of the Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) in Spinal Muscular Atrophy
by Laurey Brown, Katie Hoffman, Chiara Corbo-Galli, Siyuan Dong, Katelyn Zumpf, Christa Weigel, Colleen Blomgren, Hannah Munson, Jessa Bidwell, Vamshi Rao, Nancy L. Kuntz, Abigail Schwaede and Kristin J. Krosschell
J. Clin. Med. 2024, 13(4), 921; https://doi.org/10.3390/jcm13040921 - 6 Feb 2024
Viewed by 1047
Abstract
Background: Spinal muscular atrophy (SMA) has a remarkable impact on function and participation. Subsequently, the caregivers of individuals with SMA are impacted as well. Providers and the SMA community should be aware of the presence of and likely expectations for the existence [...] Read more.
Background: Spinal muscular atrophy (SMA) has a remarkable impact on function and participation. Subsequently, the caregivers of individuals with SMA are impacted as well. Providers and the SMA community should be aware of the presence of and likely expectations for the existence of caregiver burden. Methods: The Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) quantifies caregivers’ perceptions of function and quality of life pertaining to time, finance and emotion. Analyses were conducted among SMA types and ambulatory and ventilatory status. Participants with SMA had varying ranges of function and were on pharmaceutical treatment. Total ACEND score, longitudinal change in total ACEND score, total quality of life (QOL) score, change in total QOL score and subdomains for QOL, including time, emotion and finance, were all explored. Results: Overall, the ACEND demonstrated discriminant validity and some observed trends. Total ACEND scores improved for caregivers of those with SMA 2, remained stable longitudinally for caregivers of those with SMA 1 and 3 and were not influenced by ventilation status. The caregivers of individuals with SMA 1 had the lowest total quality of life (QOL) score, as did the caregivers of non-ambulatory individuals and those requiring assisted ventilation. Longitudinally, there were no changes in total QOL between caregivers of individuals with different SMA types or ambulatory or ventilation status. There were some differences in emotional needs, but no differences in financial impact between the caregivers of individuals with different types of SMA or ambulatory and ventilatory status. Conclusions: With this information enlightening the presence of caregiver burden and expected changes in burden with pharmaceutical treatment, providers, third party payors and the SMA community at large can better assist, equip and empower those providing the necessary assistance to enable the lives of those with SMA. Full article
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12 pages, 2740 KiB  
Article
Structured Light Plethysmography for Non-Invasive Assessment of Respiratory Pattern in Spinal Muscular Atrophy Type 1
by Noemi Brolatti, Federica Trucco, Marta Ferretti, Chiara Avanti, Paola Tacchetti, Chiara Panicucci, Pasquale Striano, Carlo Minetti, Claudio Bruno and Marina Pedemonte
J. Clin. Med. 2023, 12(24), 7553; https://doi.org/10.3390/jcm12247553 - 7 Dec 2023
Viewed by 858
Abstract
Background: Spinal muscular atrophy (SMA) type 1 is a severe condition leading to early respiratory failure. Treatment options have become available, yet respiratory outcome measures in SMA type 1 are limited. The aim of this study was to assess the respiratory pattern in [...] Read more.
Background: Spinal muscular atrophy (SMA) type 1 is a severe condition leading to early respiratory failure. Treatment options have become available, yet respiratory outcome measures in SMA type 1 are limited. The aim of this study was to assess the respiratory pattern in SMA type 1 patients via structured light plethysmography (SLP). SLP measures the thoraco-abdominal movements by projecting a light grid onto the anterior thoraco-abdominal surface. Methods: Cross-sectional study of consecutive children with SMA type 1. All children underwent motor assessment (CHOP-INTEND) and one-minute tidal breathing recording by SLP in supine position while self-ventilating in room air. The Respiratory rate, the abdominal vs. chest contribution to breath (Relative Expired Abdomen%, Relative Expired Chest%) and the severity of thoraco-abdominal paradox (Phase Angle) were acquired. Results: Nineteen patients were included, median (IQR) age 2.3 years (1.4–7.9). Their respiratory pattern captured via SLP showed a raised median (IQR) respiratory rate per age of 33.5 bpm (26.6–41.7), a prevalent abdominal contribution to tidal breathing with median (IQR) Relative Expired Abdomen 77% (68–90) vs. Chest 23% (10–32). Thoracoabdominal paradox was detected (median Phase Angle 48.70°) and its severity correlated negatively with CHOP-INTEND (r −0.8, p < 0.01). Conclusions: SLP captured and quantified the respiratory features of infants and children with SMA type 1. Full article
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18 pages, 1764 KiB  
Article
Cerebrospinal Fluid Proteomic Changes after Nusinersen in Patients with Spinal Muscular Atrophy
by Marie Beaudin, Tahereh Kamali, Whitney Tang, Katharine A. Hagerman, Sally Dunaway Young, Lisa Ghiglieri, Dana M. Parker, Benoit Lehallier, Carolina Tesi-Rocha, Jacinda B. Sampson, Tina Duong and John W. Day
J. Clin. Med. 2023, 12(20), 6696; https://doi.org/10.3390/jcm12206696 - 23 Oct 2023
Cited by 2 | Viewed by 2165
Abstract
Disease-modifying treatments have transformed the natural history of spinal muscular atrophy (SMA), but the cellular pathways altered by SMN restoration remain undefined and biomarkers cannot yet precisely predict treatment response. We performed an exploratory cerebrospinal fluid (CSF) proteomic study in a diverse sample [...] Read more.
Disease-modifying treatments have transformed the natural history of spinal muscular atrophy (SMA), but the cellular pathways altered by SMN restoration remain undefined and biomarkers cannot yet precisely predict treatment response. We performed an exploratory cerebrospinal fluid (CSF) proteomic study in a diverse sample of SMA patients treated with nusinersen to elucidate therapeutic pathways and identify predictors of motor improvement. Proteomic analyses were performed on CSF samples collected before treatment (T0) and at 6 months (T6) using an Olink panel to quantify 1113 peptides. A supervised machine learning approach was used to identify proteins that discriminated patients who improved functionally from those who did not after 2 years of treatment. A total of 49 SMA patients were included (10 type 1, 18 type 2, and 21 type 3), ranging in age from 3 months to 65 years. Most proteins showed a decrease in CSF concentration at T6. The machine learning algorithm identified ARSB, ENTPD2, NEFL, and IFI30 as the proteins most predictive of improvement. The machine learning model was able to predict motor improvement at 2 years with 79.6% accuracy. The results highlight the potential application of CSF biomarkers to predict motor improvement following SMA treatment. Validation in larger datasets is needed. Full article
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15 pages, 1856 KiB  
Article
Duchenne Muscular Dystrophy from Brain to Muscle: The Role of Brain Dystrophin Isoforms in Motor Functions
by Nalaka Wijekoon, Lakmal Gonawala, Pyara Ratnayake, Dhammika Amaratunga, Yetrib Hathout, Chandra Mohan, Harry W. M. Steinbusch, Ashwin Dalal, Eric P. Hoffman and K. Ranil D. de Silva
J. Clin. Med. 2023, 12(17), 5637; https://doi.org/10.3390/jcm12175637 - 29 Aug 2023
Cited by 4 | Viewed by 1647
Abstract
Brain function and its effect on motor performance in Duchenne muscular dystrophy (DMD) is an emerging concept. The present study explored how cumulative dystrophin isoform loss, age, and a corticosteroid treatment affect DMD motor outcomes. A total of 133 genetically confirmed DMD patients [...] Read more.
Brain function and its effect on motor performance in Duchenne muscular dystrophy (DMD) is an emerging concept. The present study explored how cumulative dystrophin isoform loss, age, and a corticosteroid treatment affect DMD motor outcomes. A total of 133 genetically confirmed DMD patients from Sri Lanka were divided into two groups based on whether their shorter dystrophin isoforms (Dp140, Dp116, and Dp71) were affected: Group 1, containing patients with Dp140, Dp116, and Dp71 affected (n = 98), and Group 2, containing unaffected patients (n = 35). A subset of 52 patients (Group 1, n = 38; Group 2, n = 14) was followed for up to three follow-ups performed in an average of 28-month intervals. The effect of the cumulative loss of shorter dystrophin isoforms on the natural history of DMD was analyzed. A total of 74/133 (56%) patients encountered developmental delays, with 66/74 (89%) being in Group 1 and 8/74 (11%) being in Group 2 (p < 0.001). Motor developmental delays were predominant. The hip and knee muscular strength, according to the Medical Research Council (MRC) scale and the North Star Ambulatory Assessment (NSAA) activities, “standing on one leg R”, “standing on one leg L”, and “walk”, declined rapidly in Group 1 (p < 0.001 In the follow-up analysis, Group 1 patients became wheelchair-bound at a younger age than those of Group 2 (p = 0.004). DMD motor dysfunction is linked to DMD mutations that affect shorter dystrophin isoforms. When stratifying individuals for clinical trials, considering the DMD mutation site and its impact on a shorter dystrophin isoform is crucial. Full article
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15 pages, 1611 KiB  
Article
Nusinersen Treatment of Children with Later-Onset Spinal Muscular Atrophy and Scoliosis Is Associated with Improvements or Stabilization of Motor Function
by Sally Dunaway Young, Jacqueline Montes, Allan M. Glanzman, Richard Gee, John W. Day, Richard S. Finkel, Basil T. Darras, Darryl C. De Vivo, Giulia Gambino, Richard Foster, Janice Wong, Steve Garafalo and Zdenek Berger
J. Clin. Med. 2023, 12(15), 4901; https://doi.org/10.3390/jcm12154901 - 26 Jul 2023
Cited by 5 | Viewed by 2007
Abstract
Nusinersen has been shown to improve or stabilize motor function in individuals with spinal muscular atrophy (SMA). We evaluated baseline scoliosis severity and motor function in nusinersen-treated non-ambulatory children with later-onset SMA. Post hoc analyses were conducted on 95 children initiating nusinersen treatment [...] Read more.
Nusinersen has been shown to improve or stabilize motor function in individuals with spinal muscular atrophy (SMA). We evaluated baseline scoliosis severity and motor function in nusinersen-treated non-ambulatory children with later-onset SMA. Post hoc analyses were conducted on 95 children initiating nusinersen treatment in the CHERISH study or SHINE long-term extension trial. Participants were categorized by baseline Cobb angle (first nusinersen dose): ≤10°, >10° to ≤20°, and >20° to <40° (no/mild/moderate scoliosis, respectively). Outcome measures included the Hammersmith Functional Motor Score—Expanded (HFMSE) and the Revised Upper Limb Module (RULM). Regression analysis determined the relationships between baseline scoliosis severity and later motor function. For children with no, mild, and moderate scoliosis, the mean increase in HFMSE from baseline to Day 930 was 6.0, 3.9, and 0.7 points, and in RULM was 6.1, 4.6, and 2.3 points. In the linear model, a 10° increase in baseline Cobb angle was significantly associated with a −1.4 (95% CI −2.6, −0.2) point decrease in HFMSE (p = 0.02) and a −1.2 (95% CI −2.1, −0.4) point decrease in RULM (p = 0.006) at Day 930. Treatment with nusinersen was associated with improvements/stabilization in motor function in all groups, with greater response in those with no/mild scoliosis at baseline. Full article
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9 pages, 264 KiB  
Article
Delayed Diagnosis of Congenital Myasthenic Syndromes Erroneously Interpreted as Mitochondrial Myopathies
by Mariana I. Muñoz-García, María Paz Guerrero-Molina, Carlos Pablo de Fuenmayor-Fernández de la Hoz, Laura Bermejo-Guerrero, Ana Arteche-López, Aurelio Hernández-Laín, Miguel A. Martín and Cristina Domínguez-González
J. Clin. Med. 2023, 12(9), 3308; https://doi.org/10.3390/jcm12093308 - 6 May 2023
Cited by 1 | Viewed by 1490
Abstract
Background: Congenital myasthenic syndromes (CMSs) and primary mitochondrial myopathies (PMMs) can present with ptosis, external ophthalmoplegia, and limb weakness. Methods: Our method involved the description of three cases of CMS that were initially characterized as probable PMM. Results: All patients were male and [...] Read more.
Background: Congenital myasthenic syndromes (CMSs) and primary mitochondrial myopathies (PMMs) can present with ptosis, external ophthalmoplegia, and limb weakness. Methods: Our method involved the description of three cases of CMS that were initially characterized as probable PMM. Results: All patients were male and presented with ptosis and/or external ophthalmoplegia at birth, with proximal muscle weakness and fatigue on physical exertion. After normal repetitive nerve stimulation (RNS) studies performed on facial muscles, a muscle biopsy (at a median age of 9) was performed to rule out congenital myopathies. In all three cases, the biopsy findings (COX-negative fibers or respiratory chain defects) pointed to PMM. They were referred to our neuromuscular unit in adulthood to establish a genetic diagnosis. However, at this time, fatigability was evident in the physical exams and RNS in the spinal accessory nerve showed a decremental response in all cases. Targeted genetic studies revealed pathogenic variants in the MUSK, DOK7, and RAPSN genes. The median diagnostic delay was 29 years. Treatment resulted in functional improvement in all cases. Conclusions: Early identification of CMS is essential as medical treatment can provide clear benefits. Its diagnosis can be challenging due to phenotypic overlap with other debilitating disorders. Thus, a high index of suspicion is necessary to guide the diagnostic strategy. Full article
19 pages, 545 KiB  
Article
2-Year Change in Revised Hammersmith Scale Scores in a Large Cohort of Untreated Paediatric Type 2 and 3 SMA Participants
by Georgia Stimpson, Danielle Ramsey, Amy Wolfe, Anna Mayhew, Mariacristina Scoto, Giovanni Baranello, Robert Muni Lofra, Marion Main, Evelin Milev, Giorgia Coratti, Marika Pane, Valeria Sansone, Adele D’Amico, Enrico Bertini, Sonia Messina, Claudio Bruno, Emilio Albamonte, Elena Stacy Mazzone, Jacqueline Montes, Allan M. Glanzman, Zarazuela Zolkipli-Cunningham, Amy Pasternak, Tina Duong, Sally Dunaway Young, Matthew Civitello, Chiara Marini-Bettolo, John W. Day, Basil T. Darras, Darryl C. De Vivo, Richard S. Finkel, Eugenio Mercuri and Francesco Muntoniadd Show full author list remove Hide full author list
J. Clin. Med. 2023, 12(5), 1920; https://doi.org/10.3390/jcm12051920 - 28 Feb 2023
Cited by 2 | Viewed by 2606
Abstract
The Revised Hammersmith Scale (RHS) is a 36-item ordinal scale developed using clinical expertise and sound psychometrics to investigate motor function in participants with Spinal Muscular Atrophy (SMA). In this study, we investigate median change in the RHS score up to two years [...] Read more.
The Revised Hammersmith Scale (RHS) is a 36-item ordinal scale developed using clinical expertise and sound psychometrics to investigate motor function in participants with Spinal Muscular Atrophy (SMA). In this study, we investigate median change in the RHS score up to two years in paediatric SMA 2 and 3 participants and contextualise it to the Hammersmith Functional Motor Scale–Expanded (HFMSE). These change scores were considered by SMA type, motor function, and baseline RHS score. We consider a new transitional group, spanning crawlers, standers, and walkers-with-assistance, and analyse that alongside non-sitters, sitters, and walkers. The transitional group exhibit the most definitive change score trend, with an average 1-year decline of 3 points. In the weakest patients, we are most able to detect positive change in the RHS in the under-5 age group, whereas in the stronger patients, we are most able to detect decline in the RHS in the 8–13 age group. The RHS has a reduced floor effect compared to the HFMSE, although we show that the RHS should be used in conjunction with the RULM for participants scoring less than 20 points on the RHS. The timed items in the RHS have high between-participant variability, so participants with the same RHS total can be differentiated by their timed test items. Full article
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9 pages, 2201 KiB  
Article
A Longitudinal Follow-Up Study of Intellectual Function in Duchenne Muscular Dystrophy over Age: Is It Really Stable?
by Daniela P. R. Chieffo, Federica Moriconi, Marika Pane, Simona Lucibello, Elisabetta Ferraroli, Giulia Norcia, Martina Ricci, Anna Capasso, Gianpaolo Cicala, Bianca Buchignani, Giorgia Coratti, Costanza Cutrona, Monia Pelizzari, Claudia Brogna, Jos G. M. Hendriksen, Francesco Muntoni and Eugenio Mercuri
J. Clin. Med. 2023, 12(2), 403; https://doi.org/10.3390/jcm12020403 - 4 Jan 2023
Cited by 3 | Viewed by 1825
Abstract
The aim of the study was to retrospectively evaluate the consistency of longitudinal findings on intellectual functioning in DMD boys and their relationship to behavioral and neuropsychiatric difficulties. The cohort included 70 patients of age 3 to 17 years with at least two [...] Read more.
The aim of the study was to retrospectively evaluate the consistency of longitudinal findings on intellectual functioning in DMD boys and their relationship to behavioral and neuropsychiatric difficulties. The cohort included 70 patients of age 3 to 17 years with at least two assessments using the Wechsler scales. CBCL and clinical observation of behavior were also performed. Changes in total intelligence quotient were interpreted as stable or not stable using the reliable-change method. On the first assessment 43/70 had normal quotients, 18 borderline, 5 mild, and 4 moderate intellectual disability, while 27/70 had no behavioral disorders, 17 had abnormal CBCL, and 26 patients had clear signs of attention deficits despite normal CBCL. The remaining seven were untestable. The mean total intelligence quotient change in the cohort was −2.99 points (SD: 12.29). Stable results on TIQ were found in 63% of the paired assessments. A third of the consecutive cognitive assessments showed a difference of more than 11 points with changes up to 42 points. Boys with no behavioral/attention disorder had smaller changes than those with attention (p = 0.007) and behavioral disorders (p = 0.002). Changes in IQ may occur in Duchenne and are likely to be associated with behavioral or attention deficits. Full article
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Review

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18 pages, 691 KiB  
Review
Measuring Fatigue and Fatigability in Spinal Muscular Atrophy (SMA): Challenges and Opportunities
by Rafael S. Rodriguez-Torres, David Uher, Emma L. Gay, Giorgia Coratti, Sally Dunaway Young, Annemarie Rohwer, Robert Muni Lofra, Darryl C. De Vivo, Michio Hirano, Nancy W. Glynn and Jacqueline Montes
J. Clin. Med. 2023, 12(10), 3458; https://doi.org/10.3390/jcm12103458 - 14 May 2023
Cited by 3 | Viewed by 3368
Abstract
Fatigue, a common symptom, together with the characteristic of performance fatigability, are well-documented features of SMA that impact quality of life and function. Importantly, establishing associations between multidimensional self-reported fatigue scales and patient performance has proven difficult. This review was conducted to evaluate [...] Read more.
Fatigue, a common symptom, together with the characteristic of performance fatigability, are well-documented features of SMA that impact quality of life and function. Importantly, establishing associations between multidimensional self-reported fatigue scales and patient performance has proven difficult. This review was conducted to evaluate the various patient-reported fatigue scales applied in SMA, with the objective of considering the limitations and advantages of each measure. Variable use of fatigue-related nomenclature, including conflicting terminology interpretation, has affected assessment of physical fatigue attributes, specifically perceived fatigability. This review encourages the development of original patient-reported scales to enable perceived fatigability assessment, providing a potential complementary method of evaluating treatment response. Full article
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Other

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15 pages, 782 KiB  
Systematic Review
Electrophysiological and Imaging Biomarkers to Evaluate Exercise Training in Patients with Neuromuscular Disease: A Systematic Review
by Lisa Pomp, Jeroen Antonius Lodewijk Jeneson, W. Ludo van der Pol and Bart Bartels
J. Clin. Med. 2023, 12(21), 6834; https://doi.org/10.3390/jcm12216834 - 29 Oct 2023
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Abstract
Exercise therapy as part of the clinical management of patients with neuromuscular diseases (NMDs) is complicated by the limited insights into its efficacy. There is an urgent need for sensitive and non-invasive quantitative muscle biomarkers to monitor the effects of exercise training. Therefore, [...] Read more.
Exercise therapy as part of the clinical management of patients with neuromuscular diseases (NMDs) is complicated by the limited insights into its efficacy. There is an urgent need for sensitive and non-invasive quantitative muscle biomarkers to monitor the effects of exercise training. Therefore, the objective of this systematic review was to critically appraise and summarize the current evidence for the sensitivity of quantitative, non-invasive biomarkers, based on imaging and electrophysiological techniques, for measuring the effects of physical exercise training. We identified a wide variety of biomarkers, including imaging techniques, i.e., magnetic resonance imaging (MRI) and ultrasound, surface electromyography (sEMG), magnetic resonance spectroscopy (MRS), and near-infrared spectroscopy (NIRS). Imaging biomarkers, such as muscle maximum area and muscle thickness, and EMG biomarkers, such as compound muscle action potential (CMAP) amplitude, detected significant changes in muscle morphology and neural adaptations following resistance training. MRS and NIRS biomarkers, such as initial phosphocreatine recovery rate (V), mitochondrial capacity (Qmax), adenosine phosphate recovery half-time (ADP t1/2), and micromolar changes in deoxygenated hemoglobin and myoglobin concentrations (Δ[deoxy(Hb + Mb)]), detected significant adaptations in oxidative metabolism after endurance training. We also identified biomarkers whose clinical relevance has not yet been assessed due to lack of sufficient study. Full article
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