Amyotrophic Lateral Sclerosis (ALS)

ANXIETY PANIC_margarita-zharova-1463319-unsplash.jpg
 
 

Amyotrophic Lateral Sclerosis (ALS) management requires multidisciplinary teams of health professionals including health psychologists, nutritionists, physical therapists and speech therapists, who work closely with physicians and nursing care, with the aim to provide enhanced health care support, improve patients overall quality of life and reduce rate of disease progress (Zarei et al., 2015).

 

ALS is a devastating, rare and progressive neuron degenerative disease that appears rather uniformely worldwide, affecting 1-2 individuals in every 100,000 population (Mitsumoto, 2009). Symptoms include limbic, bulbar, truck and respiratory weakness. The disease is causing the progressive loss of muscles, leading to difficulties in moving, speech, swallowing and respiration and can be extended to non-motor neuron degeneration, causing cognitive impairment and dementia. After appearance of the first symptoms the average survival is approximately 3 to 5 years (Zarei et al, 2015), however in some people ALS appears with a very slow progress of several decades.

 

The cause of the disease remains uncertain. Approximately 5%-10% of cases of ALS occurrence are familial and the rest are sporadic with no previous family history of the disease (Wijesekera & Leigh, 2009). Riluzole and enderavone are the only FDA approved drugs, which in clinical trials have shown that may help in prolonging survival and and improve daily functioning (Miller, Mitchell, & Moore, 2012; Takahashi, 2009). Furthermore, treatment is limited to drug prescriptions for the management of symptoms, such as cramps, excessive saliva, insomnia, anxiety, depression as also to enteral feeding and oxygen to support malnutrition and respiratory dysfunction, accordingly (Wills, 2009;  Mitsumoto, 2009). A substantial amount of research has been devoted on numerous risk factors including immunity dysfunction, neuronal metabolism dysfunction, excitoxicity, genetic abnormalities, heavy metals, toxic agents and exposure, infections, inflammation and nutritional disorders, such as vitamins deficiencies (Mitsumoto, 2009).  It has been suggested that a combination of genetic and environmental factors may trigger the disease onset (Mitsumoto, 2009).

 

Patients with ALS suffer from chronic pain. ALS secondary symptoms, such as weakness, fatigue, loss of dexterity, loss of appetite, insomnia and anxiety can mask symptoms of depression, which is highly under-diagnosed (Atassi et al., 2011). Chronic pain and pain intensity significantly influences patients’ quality of life and clinical attention to depressive symptomatology is highly recommended. It has been suggested that the influence of pain on patients’ quality of life remains only at the presence of depressive symptomatology. For example, the findings of a pilot study suggest that the worsening of the Quality of Life (QOL) of patients with intense pain occurs only in the presence of depressive symptomatology and also that depression directly deteriorates the QOL of patients with ALS; an effect irrespective of pain intensity (Pizzimenti, Aragona, Onesti, & Inghilleri, 2013).

 

In addition, clinical attention to depressive symptomatology is recommended by robust evidence from national studies for the occurrence of depression preceding ALS onset (Euesben, Danese, Lewis, & Maughan, 2017). For example, the results of a recent longitudinal study with a national sample – conducted in Sweden and included 1,752 and 8,760 controls – suggested that individuals who initially did not have ALS, but the disease was developed later, had increased risk of depression prior to the diagnosis of ALS – particularly, during the year before the diagnosis of ALS – as compared to participants in the control group. The study also found that after receiving the diagnosis of ALS, patients presented increased risk of depression, especially during the first year after (Roos et al., 2016), suggesting the need of psychological interventions and support for those patients receiving ALS diagnosis.

In terms of the contribution of dietary intake, research suggests that mitochondrial dysfunction and progressive failure to produce energy may play a key role in ALS onset and progression. There has been substantial amount of research evidence showing that Ketogenic diet – a diet that brings the metabolism in a state at which it burns fat rather than carbohydtrates – is protecting neuron cells’ energy production efficiency. Also, there has been evidence that malnutrition, which is common among ALS patients due to the difficulties that degeneration causes, plays an important role in disease progression in both humans and mice (Paganoni & Wills, 2013). Based on those findings, numerous diet animal models for ALS have been developed, intervening high daily intake in fat, 50%-60%, 20%-40% carbohydrates, 15%-20% protein and reported reduced risk of ALS and improved rate of disease progression. However, randomized control clinical trials (RCT’s) are needed to explore whether ketogenic diet can ameliorate symptoms and disease progression in humans (Zhao 2006; Paganoni & Wills, 2013). Physical activity (Pupillo et al., 2014) and Mediterranean diet rich in monosaturated fat may also be protective against the disease (Sofi, Macchi & Casini, 2013). Also, there has been some evidence from few exercise intervention trials and animal model studies that some types of exercise, may improve patients functional ability, delay decline and decrease disability, however more RCT’s are needed to explore to what extent exercise is beneficial and which types of exercise (Dal Bello-Has & Florence, 2013). Moreover, insufficient level of physical activity and avoidance may further contribute into muscle weakness, contractures and pain, as well as cause cardiovascular and respiratory dysfunction (Lunetta et al., 2016).

 

References

Atassi, N., Cook, A., Pineda, C. M. E., Yerramilli-Rao, P., Pulley, D., & Cudkowicz, M. (2011). Depression in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis, 12(2), 109-112. doi:10.3109/17482968.2010.536839

Cwick, V. A. (2009). What is Amyotrophic Lateral Sclerosis? In H. Mitsumoto (Ed.), Amyotrophic Lateral Sclerosis. A Guide for Patients and Families (pp. 3-22).New York: Demos Medical Publishing

Dal Bello-Haas V., & Florence J. M. (2013). Therapeutic exercise for people with amyotrophic lateral sclerosis ormotor neuron disease. Cochrane Database of Systematic Reviews, 5(5). doi: 10.1002/14651858.CD005229.pub3.

Euesden, J., Danese, A, Lewis, C. M, & Maughan, B. (2017). A bidirectional relationship between depression and the autoimmune disorders: New perspectives from the National Child Development Study. PLoS ONE, 12(3). doi:10.1371/journal.pone.0173015

Wijesekera, L. C., & Leigh, P. N. (2009). Amyotrophic lateral sclerosis. Orphanet Journal of rare Diseases, 4(3). doi:10.1186/1750-1172-4-3

Lunetta, C., Lizio, A.,  Sansone, V. A.,  Cellotto, N. M., Maestri, E.,  Bettinelli, M., …  Corbo, M. (2016).  Strictly monitored exercise programs reduce motor deterioration in ALS: preliminary results of a randomized controlled trial. Journal of Neurology, 263, 52-60. doi: 10.1007/s00415-015-7924-z

Miller, R., Mitchell, J. D., & Moore, D. H. (2012). Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database of Systematic Reviews, 14(3). doi: 10.1002/14651858.CD001447.pub3

Paganoni, S., & Wills, A. M., (2013). High-Fat and Ketogenic Diets in Amyotrophic Lateral Sclerosis. Journal of Child Neurology, 28(8), 989-992. doi:10.1177/0883073813488669

Pizzimenti, A., Aragona, M., Onesti, M., & Inghilleri, M. (2013). Depression, pain and quality of life in patients with amyotrophic lateral sclerosis: a cross-sectional study. Functional Neurology, 28(2), 115-119. doi: 10.11138/FNeur/2013.28.2.115.

Pupillo, E., Messina, P., G., Biold, G. G.,  Logroscino, G., Zoccolella, S., Chίo, A., … the EURALS Consortium, (2014). Physical activity and amyotrophic lateral sclerosis: a European population-based casecontrol study. Annals of Neurology, 75, 708-716. doi: 1 0.1002/ana.24150

Roos,E., Mariosa, D.,  Ingre, C., Lundholm, C.,  Wirdefeldt, K.,  Roos, P. M., & Fang, F. (2016). Depression in amyotrophic lateral sclerosis. Neurology, 86(24), 2271-7. doi: 10.1212/WNL.0000000000002671

Takahashi, R. (2009). Edaravone in ALS. Experimental Neurology, 217, 235-236. doi: 10.1016/j.expneurol.2009.03.001

Wills, A. M., Hubbard, J. Macklin, E. A., Glass, J., Tandan, R., Simpson, E. P., … the MDA Clinical Research Network, (2014). Hypercaloric enteral nutrition in Amyotrophic Lateral Sclerosis: a randomized double-blind placebo-controlled trial. Lancet, 383(9934), 2065–2072. doi:10.1016/S0140-6736(14)60222-1.

Zarei, S., Carr, K.,  Reiley, L., Diaz, K., Guerra, O., Altamirano, P. F., Chinea, A. (2015).  A comprehensive review of amyotrophic lateral sclerosis. Surgical Neurology International, 6(171). doi: 10.4103/2152-7806.169561

Sofi, F., Macchi, C., & Casini, A. (2013). Mediterranean Diet and Minimizing Neurodegeneration. Current Nutrition Reports, 2, 75-80. doi: 10.1007/s13668-013-0041-7

 
 

Numerous diet animal models for ALS report reduced risk of ALS and improved rate of disease progression when intervening with high daily intake in fat, 50%-60%, 20%-40% carbohydrates and 15%-20% protein of the daily calories amount.

However, randomized control clinical trials (RCT’s) are needed to explore whether ketogenic diet can ameliorate symptoms and disease progression in humans (Zhao 2006; Paganoni & Wills, 2013).