Neuromuscular diseases are characterised by impaired function of the skeletal muscles, which can arise from problems with muscle itself or of the peripheral nervous system (neuromuscular junction, nerve fibres, or nerve cells in the spinal cord).
Symptoms vary considerably depending on the type of neuromuscular disorder, and the individual affected. These may include muscle wasting, muscle weakness, changes in muscle tone (and associated cramps), and associated sensory disturbances (e.g. numbness).
In total, hundreds of types of neuromuscular disease have been identified, occurring in various age groups. Key examples of neuromuscular diseases include amyotrophic lateral sclerosis (ALS), myasthenia gravis, spinal muscular atrophy, and congenital muscular dystrophy (CMD).
The prevalence of the more common neuromuscular disorders considered collectively is similar to that of Parkinson’s disease and is approximately twice that of multiple sclerosis1.
Pathology and functional impact of neuromuscular disease
Factors involved in the development of neuromuscular disorders are extremely diverse and are dependent on the exact condition, and individual, considered.
Implicated factors can include genetic mutations, immune abnormalities (e.g. autoimmune reactions), metabolism (e.g. diabetes, enzyme disturbances), or exposure to certain toxins or infections1.
For example, approximately 10% of ALS cases are familial, i.e. tend to run within families; remarkably, more than 60% of variation in the expression of familial ALS can be explained by known gene mutations, such as the superoxide dismutase 1 gene mutation2.
In myasthenia gravis, the body develops antibodies directed against its own acetylcholine receptors, which sit at the neuromuscular junction; this leads to muscle weakness that worsens during activity and reverses during rest.
Research and development in neuromuscular disease
Interventions for neuromuscular diseases require a multidisciplinary approach, focusing on maximising everyday function, health, and autonomy; as well as on helping to prevent complications arising.
Research indicates that combination treatments can yield improved function, quality of life, and longer-term outcomes.
Interventions can include genetic tests/counselling, medication reviews, orthopaedic input, speech and language therapy, cardiology management, pulmonary management, psychosocial support, and rehabilitation in the broadest sense1.
Most available interventions, while helpful, unfortunately are not capable of reversing the underlying pathology of a given neuromuscular disorder.
In the laboratory, promising experimental treatments have been identified using animal and other models, including the prospect of molecular genetic therapies3-5. As novel therapeutics enter clinical trials, it will be important to identify any effects of such treatments on cognition using objective markers.
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McDonald C.M., and Fowler W.M. Jr., (2012). The role of the neuromuscular medicine and physiatry specialists in the multidisciplinary management of neuromuscular disease. Phys Med Rehabil Clin N Am. 2012 Aug;23(3):475-93.
Deenen J.C.W., et al (2015). The Epidemiology of Neuromuscular Disorders: A Comprehensive Overview of the Literature. Journal of Neuromusc Dis (2015), 2(1), 73-85.
Benchaouir R., et al (2015). Gene and splicing therapies for neuromuscular diseases. Front Biosci (Landmark Ed). 2015 Jun 1;20:1190-233.
Raaphorst J., et al (2010). The cognitive profile of amyotrophic lateral sclerosis: A meta-analysis. Amyotroph Lateral Scler. 2010;11(1-2):27-37.
- McDonald CM, Fowler WM Jr. The role of the neuromuscular medicine and physiatry specialists in the multidisciplinary management of neuromuscular disease. Phys Med Rehabil Clin N Am. 2012 Aug;23(3):475-93.
- Laferriere F, Polymenidou M. Advances and challenges in understanding the multifaceted pathogenesis of amyotrophic lateral sclerosis. Swiss Med Wkly. 2015 Jan 30;145:w14054.
- Strehle EM, Straub V. Recent advances in the management of Duchenne muscular dystrophy. Arch Dis Child. 2015 Dec;100(12):1173-7.
- Benchaouir R, Robin V, Goyenvalle A. Gene and splicing therapies for neuromuscular diseases. Front Biosci (Landmark Ed). 2015 Jun 1;20:1190-233.
- Guptill JT, Soni M, Meriggioli MN. Current Treatment, Emerging Translational Therapies, and New Therapeutic Targets for Autoimmune Myasthenia Gravis. Neurotherapeutics. 2016 Jan;13(1):118-31.