Neuromuscular disease (NMD) is a phenomenon encompassing approximately 600 rare diseases that impair muscle function (Knuijt et al. 2014).
Most of these diseases stem from a loss of communication between nerve cells (motor neurons) and voluntary muscles or skeletal muscles that, in many cases, lead to progressive muscle weakness and premature death (Larkindale et al. 2013; Bos et al. 2015). Some neuromuscular diseases affect involuntary muscles or smooth muscles and may negatively impact heart function and respiration (Benditt and Boitano 2013). Benditt and Boitano (2013) also report breathing disorders and pulmonary complications to be the leading causes of mortality among neurologic diseases. Abnormal signaling or, in some cases, complete loss of communication between neurons and muscles stems from two general pathologies where the cause of dysfunction is either direct (muscle pathology) or indirect (nerve pathology) (Anderson et al. 2016). The former affects muscles directly, whereas the latter acts on the nervous systems’ control over muscle activity and causes variable weakness of proximal (closer to the body’s torso) and distal (farther from the body’s torso) muscles (Anderson et al. 2016). Both pathologies cause a wide range of disabilities that commonly result in the following symptoms: muscle weakness, rigidity, myalgia (pain in the muscle or muscle groups), myoclonus (involuntary muscle twitching), loss of muscular control, and/or muscle atrophy or hypertrophy (Knuijt et al. 2014; Martinez et al. 2014). Neuromuscular diseases are, for the most part, regarded as degenerative, and symptoms such as spasticity (unusual muscle tightness) and paralysis are common in the advanced stages of disease. Individuals with a NMD diagnosis often experience these physical symptoms in tandem with reductions in psychosocial functioning (Bos et al. 2015). The physical symptoms associated with NMDS usually cause, or further exacerbate, existing deficits in psychosocial functioning that negatively impact patients’ health-related quality of life (HRQoL). Decreased social support, reduced self-efficacy, and daily problems coping can affect HRQoL in NMD patients (Martinez et al. 2014; Bos et al. 2015).
Prevalences of specific NMDs greatly vary and are highly diverse. The rate of incidence can range from less than 1 case per 100,000 (Ullrich Muscular Dystrophy) to as many as 1 in 1,214 (Charcot-Marie-Tooth Disease; Benatar 2006; Braathen 2012; Norwood et al. 2009). Differences found in specific prevalence over numerous studies have been attributed to various methods of assessment/evaluation, founders’ effect (lowered genetic variation in a new population established by very few individuals from a larger population), and even the underestimation of early death due to the disease (Braathen 2012; Norwood et al. 2009). Although many of the individual NMDs are in fact relatively rare, Norwood et al. (2009) found the combined prevalence of disorders to be 37 per 100,000. This high, overall prevalence signifies NMD as encompassing a much more significant proportion of patients with chronic disease than would be assumed from simply observing individual prevalences (Norwood et al. 2009). The current literature of overall NMD prevalence is scarce. The literature that does exist is very population specific and, therefore, subject to variations in result due to the heritable nature of different NMD diseases (Rasmussen et al. 2012; Norwood et al. 2009).
Despite the individual diseases being rare, NMDs incur significant costs to society. Larkindale et al. (2013) estimated a conservative estimate of the national costs for three common NMDs (amyotrophic lateral sclerosis, Duchenne muscular dystrophy, and myotonic dystrophy) to range from $1.07 to $1.4 billion per year. To mitigate the economic burden associated with NMDs, Larkindale et al. (2013) also have suggested cost-effective interventions that slow disease progression, reduce health-care requirements, and prolong mobility.
NMDs can manifest in a number of ways, but the most prevalent NMDs stem from the following causes: dysfunction of the muscle (myopathy); neuromuscular junction, also known as the motor neurons point of communication with the muscle fiber (referred to as myasthenia); peripheral nerve (neuropathy); or anterior nerve cells (neuronapathy; Bos et al. 2015; Phillips et al. 2009). The specific causes of many neuromuscular diseases, however, remain ambiguous. Despite this elusiveness, most neuromuscular diseases are caused by single-gene mutations (Fratta and Hanna 2015). In fact, advances in genetic research have elucidated the molecular mechanisms underlying many neuromuscular diseases (Fratta and Hanna 2015). Researchers now suspect that even sporadic neuromuscular diseases, such as amyotrophic lateral sclerosis (ALS), are heritable to some degree (Chio and Lauria 2015). Whatever the cause, many neuromuscular diseases exhibit a high degree of symptom homogeneity and can manifest at birth or later in life (Knuijt et al. 2014).
Various manifestations of NMD warrant diverse and interdisciplinary treatment, making accurate diagnosis essential to tailoring effective treatments that address the needs of individual patient characteristics and produce more favorable outcomes (Chio and Lauria 2015). It is worth noting that treatments for neuromuscular diseases often focus on the management of the NMD by improving patients’ mobility, quality of life, coping, and longevity rather than recovery (Kley et al. 2013). New therapies commonly aim to stymie progression rather than reverse tissue damage (Morrow et al. 2016). Initially, comprehensive neurological examinations are necessary in the evaluation of NMDs (Frazer et al. 2013). Such examinations may include direct clinical observation, biochemical testing, isokinetic testing, nerve conduction analysis, and genetic/molecular testing (Frazer et al. 2013; El Mhandi and Bethoux 2013). Muscle biopsies can indicate classic dystrophic changes associated with NMDs, and walking tests are often used to measure walking capabilities, treatment efficacy, and disease progression (Frazer et al. 2013; Anderson et al. 2016). The measurement of muscle electrical activity, or electromyography (EMG), and nerve conduction studies fall under the category of electrodiagnostic medicine testing. Such testing often serves as an effective diagnostic tool for most neuromuscular diseases (Loseth and Torbergsen 2013). Loseth and Torbergsen (2013) also note that EMG is the most valuable method for assessing myopathy and neurography, while direct imaging of nerves is most informative for neuropathy and is a complementary method for assessing patients with severe NMDs.
With advances in neuroimaging technology, many clinicians have turned to diagnostic imaging as an identification method as well. This method is especially effective when a stroke, tumor, or other anatomical abnormalities are thought to be the primary cause of the disease. Morrow et al.’ (2016) investigation of the comparative responsiveness, validity, and sensitivity of MRI indices supports the use of MRI outcome measures to monitor intramuscular fat accumulation and reduction of muscle fluid retention, both of which are common pathological processes associated with NMDs. It should also be noted that because many neuromuscular diseases are heritable, genetic/molecular testing can be useful to diagnose or predict the risk of disease inheritance. Genetic testing for NMDs during pregnancy often results in a prenatal diagnosis that may lead to subsequent planning that can increase therapeutic effectiveness as well as medical care for patients and caregivers (Frazer et al. 2013). In addition, Frazer et al. (2013) note that many NMDs affect women of childbearing age. Pregnant women with an NMD face substantial risk for pregnancy complications, in addition to increasing the heritable risk of the particular NMD to a child.
The overall heterogeneity of NMD etiology creates a variety of treatments that are equally diverse. In fact, pathogenesis diversity pervades not just the broad category of NMDs but even the individual disorders. The absence of a comprehensive understanding of the cause of NMDs presents a major obstacle in creating effective comprehensive treatments and, indeed, suggests the necessity of tailoring treatments to the individual needs of the patient (Chio and Lauria 2015; Benatar 2006). Unfortunately, due to the deficient comprehension of the pathology of NMDs, many of the current treatments and therapies in use lack proper evidence-based empirical support (Benatar 2006; Cup et al. 2011). The general palliative treatments that are empirically supported include physical exercise, ventilators, pharmacological interventions, pain management, and various surgeries (Benatar 2006; Kley et al. 2013). The specific treatments employed are entirely dependent upon the individual disorder and the symptoms presented, as certain treatments can yield adverse effects from one disorder but prove beneficial in another (Kley et al. 2013). In more recent years, research for disease-modifying genetic therapies has begun to receive more attention as an effort to target the molecular defects at the root of the disorders (Douglas and Wood 2013). Finally, many clinical researchers cite the lack of high-quality data as being the greatest disadvantage in better understanding the etiology, treatment, and prognosis of many NMDs. Common problems in such clinical research include low recruitment due to rarity of NMDs, the selection of a specific NMD to examine, limited clinician understanding of clinical research methodologies, and a lack of responsive outcome measures to assess treatment effectiveness in clinical trials (Benatar 2006; Morrow et al. 2016).
References and Further Reading
- Chio, A., & Lauria, G. (2015). Degenerative neuromuscular diseases: Crucial gene and cell machinery discoveries. Round-up, 15, 12–13.Google Scholar
- Cup, E. C., Pieterse, A. J., Hendricks, H. T., van Engelen, B. M., Oostendorp, R. B., & van der Wilt, G. J. (2011). Implementation of multidisciplinary advice to allied health care professionals regarding the management of their patients with neuromuscular diseases. Disability & Rehabilitation, 33(9), 787–795.CrossRefGoogle Scholar
- Fratta, P., & Hanna, M. G. (2015). Neuromuscular diseases: Progress in gene discovery drives diagnostics and therapeutics. Round-up, 14, 13–14.Google Scholar
- Kley, R. A., Tarnopolsky, M. A., & Vorgerd, M. (2013). Creatine for treating neuromuscular disorders. The Cochrane Library, 6, 1361–6137.Google Scholar
- Knuijt, S., Kalf, J., de Swart, B., Drost, G., Hendricks, H., Geurts, A., & van Engelen, B. (2014). Dysarthria and dysphagia are highly prevalent among various types of neuromuscular diseases. Disability and Rehabilitation, 36(15), 1285–1289. https://doi.org/10.3109/09638288.2013.845255.CrossRefPubMedGoogle Scholar
- Martinez, O., Jometon, A., Perez, M., Lazaro, E., Amayar, I., Lopez-Paz, J. F., Oliva, M., Parada, P., Berrocoso, S., Iglesias, A., Cabarello, P., Martinez, L., & Barcena, J. E. (2014). Effectiveness of teleassistance at improving quality of life in people with neuromuscular diseases. Spanish Journal of Psychology, 17(86), 1–9.Google Scholar
- Norwood, F. L. M., Harling, C., Chinnery, P. F., Eagle, M., Bushby, K., & Straub, V. (2009). Prevalence of genetic muscle disease in Northern England: In-depth analysis of a muscle clinic population. Brain, 132(11), 3175–3186. https://doi.org/10.1093/brain/awp236.CrossRefPubMedPubMedCentralGoogle Scholar
- Phillips, M., Flemming, N., & Tsintzas, K. (2009). An exploratory study of physical activity and perceived barriers to exercise in ambulant people with neuromuscular disease compared with unaffected controls. Clinical Rehabilitation, 23(8), 746–755. https://doi.org/10.1177/0269215509334838.CrossRefPubMedGoogle Scholar
- Rasmussen, M., Risberg, K., Vøllo, A., & Skjeldal, O. H. (2012). Neuromuscular disorders in children in South-Eastern Norway. Journal of Pediatric Neurology, 10(2), 95–100.Google Scholar