Odair Henrique Gaverio Diniz*

Ms, Programa de Pós-graduação em Ciências da Cirurgia, FCM, UNICAMP, Campinas, São Paulo, Brazil

*Corresponding Author: Odair Henrique Gaverio Diniz, Ms, Programa de Pós-graduação em Ciências da Cirurgia, FCM, UNICAMP, Campinas, São Paulo, Brazil.

Received: February 18, 2026; Published: March 31, 2026

Abstract

Background: Respiratory failure remains the leading cause of morbidity and mortality across a spectrum of neuromuscular disorders (NMDs), ranging from central nervous system pathologies to primary muscle degenerations. Recent advancements in disease-modifying therapies (DMTs) and molecular interventions have fundamentally altered the natural history of these conditions.

Objective: This review aims to synthesize the respiratory pathophysiological mechanisms of Parkinson’s Disease (PD), Multiple Sclerosis (MS), Myasthenia Gravis (MG), Amyotrophic Lateral Sclerosis (ALS), Spinal Muscular Atrophy (SMA), and Duchenne Muscular Dystrophy (DMD), emphasizing the transition from palliative management to active functional preservation.

Methods: A comprehensive literature review was conducted, focusing on diagnostic gold standards (e.g., McDonald Criteria for MS, genetic testing for SMA), pulmonary function testing (PFT) nuances, and the impact of novel pharmacological agents such as antisense oligonucleotides, gene therapies, and immunomodulators.

Results: The pathophysiology of NMDs is characterized by a complex interplay between muscle weakness, bulbar dysfunction, and autonomic dysregulation. In PD and ALS, respiratory impairment often precedes overt clinical symptoms. In SMA and DMD, novel therapies (e.g., Risdiplam, Eteplirsen) demonstrate a "dissociation effect," where muscle strength is stabilized despite a continued decline in lung volume due to skeletal complications. Furthermore, immunomodulatory insights in GBS and ALS provide new targets for reducing mechanical ventilation dependence.

Conclusion: Modern respiratory management of NMDs requires an integrative approach that combines proactive ventilatory support with early molecular intervention. Understanding the specific respiratory trajectories of each phenotype is crucial for optimizing clinical outcomes and patient autonomy in the era of precision medicine.

Keywords: Neuromuscular Diseases; Respiratory Insufficiency; Disease-Modifying Therapies; Amyotrophic Lateral Sclerosis; Spinal Muscular Atrophy; Pulmonary Function Tests; Gene Therapy; Non-invasive Ventilation

References

1. Benditt JO and Boitano LJ. “Pulmonary Issues in Patients with Chronic Neuromuscular Disease. American Journal of Respiratory and Critical Care Medicine”. American Thoracic Society10 (2013): 1046.
2. Racca F., et al. “Practical approach to respiratory emergencies in neurological diseases”. Neurological Sciences. Springer Science+Business Media3 (2019): 497.
3. Patel N., et al. “Methods and Applications in Respiratory Physiology: Respiratory Mechanics, Drive and Muscle Function in Neuromuscular and Chest Wall Disorders”. Frontiers in Physiology. Frontiers Media 13 (2022): 838414.
4. Bourke SC. “Respiratory involvement in neuromuscular disease”. Clinical Medicine1 (2014): 72.
5. Bourke SC and Gibson G. “Sleep and breathing in neuromuscular disease”. European Respiratory Journal. European Respiratory Society6 (2002): 1194.
6. Chidambaram AG., et al. “Sleep Disordered Breathing in Children with Neuromuscular Disease”. Multidisciplinary Digital Publishing Institute 10.10 (2023): 1675.
7. Cho A. “Neuromuscular diseases: genomics-driven advances”. Genomics and Informatics. Korea Genome Organization 1 (2024): 24.
8. Zambon AA., et al. “Molecular mechanisms and therapeutic strategies for neuromuscular diseases”. Cellular and Molecular Life Sciences. Springer Nature1 (2024): 198.
9. Asci F., et al. “Rigidity in Parkinson’s disease: evidence from biomechanical and neurophysiological measures”. Brain9 (2023): 3705.
10. González-Usigli H., et al. “Neurocognitive Psychiatric and Neuropsychological Alterations in Parkinson’s Disease: A Basic and Clinical Approach”. Brain Sciences. Multidisciplinary Digital Publishing Institute3 (2023): 508.
11. Lee J and Muzio MR. “Neuroanatomy, Extrapyramidal System”. StatPearls (2020).
12. Kaczyńska K., et al. “Respiratory Abnormalities in Parkinson’s Disease: What Do We Know from Studies in Humans and Animal Models?” International Journal of Molecular Sciences. Multidisciplinary Digital Publishing Institute7 (2022): 3499.
13. Trevizan‐Baú, et al. “Forebrain projection neurons target functionally diverse respiratory control areas in the midbrain, pons, and medulla oblongata”. The Journal of Comparative Neurology 529.9 (2020): 2243.
14. Guerreiro CF., et al. “Função respiratória em indivíduos com e sem doença de Parkinson”. Revista Neurociências 30 (2022): 1.
15. Rahimi F., et al. “Effective management of upper limb parkinsonian tremor by incobotulinumtoxin A injections using sensor-based biomechanical patterns”. Tremor Other Hyperkinet Mov (N Y) 5 (2015): 348.
16. Axelerad AD., et al. “Respiratory Dysfunctions in Parkinson’s Disease Patients”. Brain Sciences. Multidisciplinary Digital Publishing Institute5 (2020): 595.
17. Maciel FL., et al. “Correlação entre a capacidade respiratória e a capacidade funcional em pacientes com doença de Parkinson”. Revista Eletrônica Acervo Saúde 51 (2020).
18. D’Arrigo A., et al. “Respiratory dysfunction in Parkinson’s disease: a narrative review”. ERJ Open Research. European Respiratory Society4 (2020): 165.
19. Duarte GP., et al. “Análise da mobilidade toracoabdominal de idosos com doença de parkinson, submetidos ao treinamento funcional, bicicleta estacionária e exergame: um ensaio clínico randomizado”. Revista de Ciências Médicas e Biológicas3 (2019): 325.
20. Guessoum A., et al. “The biological basis of Parkinson’s disease: A comprehensive review”. International Journal of Science and Research Archive2 (2024): 2685.
21. Chen Y., et al. “Non-Genetic Risk Factors for Parkinson’s Disease: An Overview of 46 Systematic Reviews”. Journal of Parkinson s Disease. IOS Press3 (2021): 919.
22. Polito L., et al. “Genetic Profile, Environmental Exposure, and Their Interaction in Parkinson’s Disease”. Parkinson s Disease. Hindawi Publishing Corporation (2016): 1.
23. Tsalenchuk M., et al. “Linking environmental risk factors with epigenetic mechanisms in Parkinson’s disease”. npj Parkinson s Disease. Nature Portfolio1 (2023): 123.
24. Petkova‐Kirova P., et al. “SNPs in cytochrome P450 genes decide on the fate of individuals with genetic predisposition to Parkinson’s disease”. Frontiers in Pharmacology 14 (2023): 1244516.
25. Hall A., et al. “Genetic Risk Profiling in Parkinson’s Disease and Utilizing Genetics to Gain Insight into Disease-Related Biological Pathways”. International Journal of Molecular Sciences. Multidisciplinary Digital Publishing Institute19 (2020): 7332.
26. Rizek P., et al. “An update on the diagnosis and treatment of Parkinson disease”. Canadian Medical Association Journal. Canadian Medical Association 188 (16) (2016): 1157.
27. Morris HR., et al. “The pathogenesis of Parkinson’s disease”. The Lancet. Elsevier BV10423 (2016): 293.
28. Höglinger GU., et al. “A biological classification of Parkinson’s disease: the SynNeurGe research diagnostic criteria”. The Lancet Neurology. Elsevier BV2 (2024): 191.
29. Hopfner F., et al. “Definition and diagnosis of Parkinson’s disease: guideline “Parkinson’s disease” of the German Society of Neurology”. Journal of Neurology11 (2024): 7102.
30. Malek N., et al. “Utility of the new Movement Disorder Society clinical diagnostic criteria for Parkinson’s disease applied retrospectively in a large cohort study of recent onset cases”. Parkinsonism and Related Disorders 40 (2017): 40.
31. Postuma RB., et al. “MDS clinical diagnostic criteria for Parkinson’s disease”. Movement Disorders. Wiley; 12 (2015): 1591.
32. Murphy KT and Lynch GS. “Impaired skeletal muscle health in Parkinsonian syndromes: clinical implications, mechanisms and potential treatments”. Journal of Cachexia Sarcopenia and Muscle. Springer Science+Business Media 5 (2023): 1987.
33. Adam H., et al. “An update on pathogenesis and clinical scenario for Parkinson’s disease: diagnosis and treatment”. 3 Biotech. Springer Science+Business Media5 (2025).
34. Stoessl AJ., et al. “Imaging insights into basal ganglia function, Parkinson’s disease, and dystonia”. The Lancet. Elsevier BV9942 (2014): 532.
35. Cabreira V and Massano J. “Doença de Parkinson: Revisão Clínica e Atualização”. Acta Médica Portuguesa. Ordem dos Médicos10 (2019): 661.
36. Ventura S de A., et al. “Agravamento do sintoma depressão em pacientes com Doença de Parkinson na pandemia da COVID-19: uma revisão sistemática”. Revista Eletrônica Acervo Saúde 12 (2022).
37. Meca‐Lallana V., et al. “Deciphering Multiple Sclerosis Progression”. Frontiers in Neurology. Frontiers Media; (2021): 12.
38. Pérez‐Cerdá, et al. “The link of inflammation and neurodegeneration in progressive multiple sclerosis”. Multiple Sclerosis and Demyelinating Disorders 1.1 (2025).
39. Ramar K., et al. “Sleep is essential to health: an American Academy of Sleep Medicine position statement”. Journal of Clinical Sleep Medicine 10 (2021): 2115.
40. Schwenkenbecher P., et al. “Impact of the McDonald Criteria 2017 on Early Diagnosis of Relapsing-Remitting Multiple Sclerosis”. Frontiers in Neurology. Frontiers Media 10 (2019).
41. Thompson AJ., et al. “Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria”. The Lancet Neurology. Elsevier BV 2 (2017): 162.
42. Caldatto C., et al. “Fortalecimento da musculatura expiratória na esclerose múltipla: relato de caso”. Revista FisiSenectus 2 (2016): 25.
43. Ruiz‐Delgado GJ., et al. “Respiratory impairment in persons with multiple sclerosis: A cross-sectional study”. Medicina Universitaria4 (2019).
44. Simões JLB., et al. “Anti-inflammatory Therapy by Cholinergic and Purinergic Modulation in Multiple Sclerosis Associated with SARS-CoV-2 Infection”. Molecular Neurobiology. Springer Science+Business Media10 (2021): 5090.
45. Brück W., et al. “Therapeutic Decisions in Multiple Sclerosis”. JAMA Neurology. American Medical Association (2013).
46. Catâneo AJM., et al. “Thymectomy in nonthymomatous myasthenia gravis - systematic review and meta-analysis”. Orphanet Journal of Rare Diseases. BioMed Central1 (2018).
47. Pardini E., et al. “Somatic mutations of thymic epithelial tumors with myasthenia gravis”. Frontiers in Oncology 13 (2023): 1224491.
48. Scopelliti G., et al. “Respiratory dysfunction as first presentation of myasthenia gravis misdiagnosed as COVID-19”. Neurological Sciences12 (2020): 3419.
49. Hulse EJ., et al. “Respiratory Complications of Organophosphorus Nerve Agent and Insecticide Poisoning. Implications for Respiratory and Critical Care”. American Journal of Respiratory and Critical Care Medicine American Thoracic Society12 (2014): 1342.
50. Schneider‐Gold C and Gilhus NE. “Advances and challenges in the treatment of myasthenia gravis”. Therapeutic Advances in Neurological Disorders. SAGE Publishing 14 (2021).
51. Melzer N., et al. “Clinical features, pathogenesis, and treatment of myasthenia gravis: a supplement to the Guidelines of the German Neurological Society”. Journal of Neurology. Springer Science+Business Media8 (2019): 1473.
52. Dresser L., et al. “Myasthenia Gravis: Epidemiology, Pathophysiology and Clinical Manifestations”. Journal of Clinical Medicine. Multidisciplinary Digital Publishing Institute11 (2021): 2235.
53. Godoy DA., et al. “The myasthenic patient in crisis: an update of the management in Neurointensive Care Unit”. Arquivos de Neuro-Psiquiatria. Thieme Medical Publishers (Germany) 71 (2013): 627.
54. Gilhus NE. “Myasthenia gravis, respiratory function, and respiratory tract disease”. Journal of Neurology. Springer Science+Business Media7 (2023): 3329.
55. Dimachkie MM., et al. “Guillain-Barré Syndrome and Variants”. Neurologic Clinics4 (2025): 743.
56. McKenzie E., et al. “Risk Stratification and Management of Acute Respiratory Failure in Patients With Neuromuscular Disease”. Critical Care Medicine. Lippincott Williams & Wilkins11 (2024): 1781.
57. Roodbol J., et al. “Predicting respiratory failure and outcome in pediatric Guillain-Barré syndrome”. European Journal of Paediatric Neurology 44 (2023): 18.
58. Masrori P and Damme PV. “Amyotrophic lateral sclerosis: a clinical review”. European Journal of Neurology. Wiley10 (2020): 1918.
59. Bernardo N., et al. “Autonomic nervous system and mediating role of respiratory function in patients with ALS”. Scientific Reports1 (2025): 10513.
60. Sennfält S., et al. “Respiratory function, survival, and NIV prevalence over time in ALS - a PRECISION ALS study”. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration 26 (2025): 61.
61. Štětkářová I and Ehler E. “Diagnostics of Amyotrophic Lateral Sclerosis: Up to Date”. Multidisciplinary Digital Publishing Institute 11.2 (2021): 231.
62. Zhang R., et al. “Respiratory Function Improvement and Lifespan Extension Following Immunotherapy with NP001 Support the Concept That Amyotrophic Lateral Sclerosis (ALS) Is an Immuno-Neurologic Disease”. International Journal of Molecular Sciences9 (2025): 4349.
63. Alves B., et al. “Type-1 spinal muscular atrophy cohort before and after disease-modifying therapies”. Arquivos de Neuro-Psiquiatria11 (2024): 1.
64. Boentert M., et al. “Respiratory involvement in neuromuscular disorders”. Current Opinion in Neurology. Lippincott Williams & Wilkins5 (2017): 529.
65. Finkel RS., et al. “Diagnosis and management of spinal muscular atrophy: Part 2: Pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics”. Neuromuscular Disorders3 (2017): 197.
66. Arets HGM and Ent CK van der. “Measurements of airway mechanics in spontaneously breathing young children”. Paediatric Respiratory Reviews. Elsevier BV1 (2004): 77.
67. Rochman M., et al. “Respiratory effects of nusinersen treatment in pediatric patients with spinal muscular atrophy types 2 and 3”. European Journal of Pediatrics11 (2025): 702.
68. Lagae L., et al. “Respiratory morbidity in patients with spinal muscular atrophy—a changing world in the light of disease-modifying therapies”. Frontiers in Pediatrics 12 (2024): 1366943.
69. Sansone V., et al. “1st Italian SMA Family Association Consensus Meeting: Neuromuscular Disorders”. 25.12 (2015): 979.
70. Ioos C., et al. “Respiratory Capacity Course in Patients With Infantile Spinal Muscular Atrophy”. CHEST Journal3 (2004): 831.
71. Piepers S., et al. “A natural history study of late onset spinal muscular atrophy types 3b and 4”. Journal of Neurology9 (2008): 1400.
72. Kaufmann P., et al. “Prospective cohort study of spinal muscular atrophy types 2 and 3”. Neurology 18 (2012): 1889.
73. Ribero VA., et al. “Systematic Literature Review of the Natural History of Spinal Muscular Atrophy”. Lippincott Williams & Wilkins 101.21 (2023).
74. Kant‐Smits K., et al. “Respiratory muscle fatigability in patients with spinal muscular atrophy”. Pediatric Pulmonology12 (2022): 3050.
75. Iterbeke L and Claeys KG. “Two-year Risdiplam treatment in adults with spinal muscular atrophy: improvements in motor and respiratory function, quality of life and fatigue”. Neuromuscular Disorders 52 (2025): 105397.
76. Vaillend C., et al. “Duchenne muscular dystrophy: recent insights in brain related comorbidities. Nature Communications”. Nature Portfolio1 (2025): 1298.
77. Coratti G., et al. “Age, corticosteroid treatment and site of mutations affect motor functional changes in young boys with Duchenne Muscular Dystrophy”. PLoS ONE7 (2022).
78. Chesshyre M., et al. “Dystrophin isoform deficiency and upper‐limb and respiratory function in Duchenne muscular dystrophy”. Developmental Medicine and Child Neurology10 (2025): 1280.
79. Poyatos‐García J., et al. “Deletion of exons 45 to 55 in the DMD gene: from the therapeutic perspective to the in vitro model”. Skeletal Muscle1 (2024).

Citation

Citation: Odair Henrique Gaverio Diniz. “Current Topics on Respiratory Physiopathology in Neuromuscular Diseases". Acta Scientific Neurology 9.4 (2026): 27-37.

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Copyright: ©2026 Odair Henrique Gaverio Diniz. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.