Amyotrophic Lateral disease, also known as Lou Gehrig’s disease, is a neuromuscular disease that is caused by degeneration of motor nerve cells in the brain and in the spinal cord. It leads to progressive muscle weakness and dysfunction of the medulla oblongata causing patients issues with transmitting signals from their brain to their spinal cord and vice versa. The patients that are affected by ALS have hypothalamic atrophy which results in a decrease in many necessary hormones such as orexin, oxytocin and TDP- 43. The hormone orexin is responsible for wakefulness and appetite while the hormone oxytocin is responsible for appetite and hunger. TDP- 43 is a protein responsible for processing molecules that make mRNA.
In majority of patients with ALS, Hypothalamic atrophy is observed. This means that these patients have progressive degeneration of their hypothalamus which causes major issues for them. The hypothalamus plays an important role in the human body as it controls eating behavior, with an appetite stimulating pathway and can also suppress appetite in an individual with a pathway that acts on neurons. The problem in patients with ALS is that their bodies tend to gear towards a lower appetite because of the hypothalamic atrophy that they are affected by. This paper by Gabery et. al, looks into hypothalamic atrophy in patients with ALS using volumetric analysis of MR images and correlates it with their BMI to try and find a connection between the two. This signifies that there is an impact (a lower BMI in patients with ALS than the control group of individuals without ALS) on how the atrophy of the Hypothalamus effects those affected. It was then looked at again to confirm these findings of a reduction of hypothalamus volume of those with ALS using stereological analyses of post mortem brain tissue.
Another issue in patients with ALS is the loss of oxytocin producing neurons in the PVN (paraventricular nucleus of the hypothalamus) and orexin producing neurons in the lateral hypothalamus. This is thought to aid in the consistent muscle wasting in those patients affected and due to the issues in the spinal cord and the brain it is not advised that these patients exercise or it can have dire consequences to them and their bodies in the long run.
The loss of orexin in patients with ALS is high but does not affect them as much as patients with narcolepsy. However there still are many reports in individuals with ALS of issues with staying in REM sleep and issues of falling asleep in general. The paper by Gabery et al., describes that patient with ALS have shown a correlation between the drop in levels of orexin and significant changes to their circadian rhythms. There is also a change in patients paraventricular thalamus, which is the region that is responsible for wakefulness control. So, while these patients have a hard time staying asleep, they also have a hard time staying awake as well.
With all of these issues individuals that become diagnosed with ALS usually only live for about two to five years. More research and effort on figuring out the disease has extended the life expectancy a bit to ten years. More research and more time do need to be spent on how to prevent this disease from happening and how to help individuals that are diagnosed with ALS cope with it. If there was more focus on the hypothalamus atrophy done there may be a few ways to prevent this disease from occurring. There are many ways hypothalamic atrophy can occur some being anemia, a genetic disorder, a tumor, head trauma, etc. If there was more time spent on checking patient’s hypothalamus that have gone through a major surgery or major hospital visit before they left it is a possibility this disease could be prevented.
Gabery, S., Ahmed, R. M., Caga, J., Kiernan, M. C., Halliday, G. M., & Petersen, A. (2021, March 23). Loss of the metabolism and sleep regulating neuronal populations expressing orexin and oxytocin in the hypothalamus in amyotrophic lateral sclerosis. Neuropathology and Applied Neurobiology. Retrieved March 1, 2022, from https://onlinelibrary.wiley.com/doi/10.1111/nan.12709
