When neurons malfunction...
- Keerthi Nalabotu
- Jul 16, 2020
- 6 min read
Updated: Jul 19, 2020
Imagine not being able to control how you chew food or even the saliva in your own mouth. Imagine staring at your hand as it twitches uncontrollably. Imagine growing weaker every day, but not knowing why. Imagine being told that your loved one may not live after 4 years.
Image by Gerd Altmann from Pixabay
As horrible as these situations may sound, they, unfortunately, are true for 2 in every 100,000 people. Sue, a 54-year-old woman, was diagnosed with Motor Neuron Disease (MND). Not only was she given a death sentence, but her family was hurt to the core. Sue was not only a sister, but also a daughter, and a friend to everyone around her. They were with her all the way to the end, encouraging her and reminding her of old stories, but in the end, they knew that there was no hope left.
So.... What is MND?
Motor Neuron Disorders cause neural cells that control movement to degrade. In normal circumstances, signals are transported from the upper motor neurons to the lower motor neurons. However, when someone has an MND, there are disruptions between these signals. The lag of these signals may cause muscles to stiffen, weaken, and uncontrollably twitch. MNDs occur in all ages. The causes of MNDs, however, are mostly unknown. Around 10-15% of all MND cases are familial (inherited). However, the rest are sporadic (not inherited). MND is not one disease, rather, it is a whole category of neurodegenerative disorders. It includes various disorders within itself, several of which this article will go over in detail.
Image by Gordon Johnson from Pixabay
The brain has more to do with the muscles that you possibly imagine!
What are the types of MNDs?
The most common MND is Amyotrophic Lateral Sclerosis (ALS) which affects more than 30,000 people at any given time in the US. Most of you may know Stephen Hawking, a revolutionary physicist. However, he was also an ALS patient who defied death for more time than one could have imagined. Most people who have ALS are told that they may not survive for more than 3 to 5 years. In rare cases, the patient may survive for 10 or more years. 90% of all ALS cases are sporadic and they mostly occur in men, like most other MNDs. In the other 10% of cases that are familial, it has been shown that there are 15-disease causing genes. The most common defect occurs in a gene known as “chromosome 9 open reading frame 72” (C9ORF72). Most ALS patients experience stiffness and weakening of various muscles, including the bulbar muscles (mouth and throat muscles responsible for talking, speaking, swallowing, etc.).
Another MND is Spinal Muscular Atrophy (SMA), which is a rare inherited disease that is one of the most frequent causes of infant mortality. SMA is caused by a defect in the SMN1 gene, which results in decreased production of the SMN (Survival Motor Neuron) protein. The SMN protein plays roles in cellular trafficking and RNA development, including the transport and regulation of mitochondrial activity. When there is a decreased performance in this protein, the muscles weaken due to lower motor neuron deterioration. SMA is a very serious disorder that is divided into 3 types based on age, severity, and progression.
Image by: Gordon Johnson from Pixabay
Proximal SMA 1 (Werdnig-Hoffmann disease):
Noticed by the time a child is 6 months old.
Scoliosis may develop (spine curves abnormally)
Difficulty breathing, swallowing, motor degradation, etc.
Most kids died by 1 year of age (before treatments were discovered).
Autosomal Recessive Inheritance
Reflexes slow down
SMA 2:
6-18 months old
Difficulty breathing
Can’t walk or stand
SMA 3 (Kugelberg-Welander disease):
2-17 years old
Problem walking
Lower limbs affected
Sometimes, neurologists may need time to diagnose a certain disease due to the similarities present between the various MNDs. For example, Primary Lateral Sclerosis (PLS) is an upper motor neuron disease. However, over time, it may develop into a lower motor neuron disease, becoming ALS. For this reason, neurologists may observe the disease’s progression over a few years in order to make sure the diagnosis was correct. PLS is not a fatal disease and the cause is still unknown. PLS causes muscle wasting and weakness. Breathing can be hard as well.
The last MND I’ll go over in this blog article is Progressive Bulbar Palsy (PBP), which is also known as Progressive Bulbar Atrophy. PBP attacks lower motor neurons that are connected to the brain stem. It causes weakness in the bulbar muscles (as indicated by the name). This results in the inability to speak, chew, and swallow. Sometimes, the patients may choke on their own food and saliva due to the weakening muscles. They may also have random emotional changes, which is called the pseudobulbar affect.
How are MNDs diagnosed?
Along with knowing these Motor Neuron diseases, it’s important to note how they’re diagnosed since most of these disorders are similar to other muscle degrading disorders. Here are a few different procedures used to diagnose MND diseases:
Image by mohamed Hassan from Pixabay
The picture above is a simplified version of an MRI.
Electromyography: A recording instrument attached to a thin needle electrode is placed in the muscle. The instrument records electrical activity. If there are abnormal electrical signals, it means that there has been damage in the motor neurons.
Nerve Conduction Study: This study is often done in conjunction with Electromyography. Small jolts of electricity are sent through the skin using tiny electrodes. The electrical signals received can be read using a recording machine and using the nerve conduction study, one can assess whether there are any abnormalities in sensory nerves.
Laboratory tests: Can assess whether the patient has a muscle disease or an MND since both categories of diseases have similar symptoms. These tests use various types of fluids including blood, urine, and brain fluid.
Magnetic Resonance Imaging (MRI’s): Can help rule out certain problems like tumors, infections, inflammations, strokes, etc.
Muscle/Nerve Biopsies: Sample of a muscle is taken out using a hollow needle. The sample is then tested. However, this process is deemed unnecessary by many neurologists.
Is there a cure?
Well, as long as we have a few cures, we’re fine… right? Hypothetically, having a cure would be amazing, but that isn’t a luxury we have today. There are no true cures for MNDs, rather most medicines and drugs just slow the progression of the disease, or lessen the pain. Drugs like Riluzole can’t reverse the damage done by a disease, but it can increase a patient’s life span by about 10%. Riluzole allows for protection of the damaged motor neurons by reducing the release of glutamate and blocking the sodium ion channels. Nusinersen, another promising medicine, was approved by the FDA in 2016 for both children and adults. Nusinersen is a type of antisense oligonucleotide which is used to treat SMA by increasing the SMN protein. Other drugs include Onasemnogeme abeparovec-xioi, muscle relaxers, botulinum toxin, etc.
Image by Kendal from Unsplash
Why is this important? We have yet to find a real cure for MNDs. As of now the research being done on MNDs is very extensive, with private organizations and government organizations alike working to understand the complexities of MNDs. Like HIV, Cancer, and other Neurodegenerative diseases like Alzheimer’s, we may never truly understand everything about MNDs. However, we can try. As of now, the National Institute of Neurological Disorders and Stroke (NINDS) is researching anti-sense oligonucleotides as potential drugs, since they block and correct RNA molecules which connect genes and proteins. Stem cell research is also being done since stem cells can transform into any cell including motor neurons. There’s also research being performed on autologous mesenchymal stem cells which are made from a person’s own bone marrow and injected into the cerebrospinal fluid. MSC stimulates high levels of neurotrophic factors (NTFs) which help in creating neuronal growth.
No matter how we look at it, we have to realize two major aspects of these diseases. They aren’t controllable and they aren’t yet curable. Control and cure. These are what we have to focus on in the future. For aspiring scientists and neurologists, MNDs will certainly be a principal region of research. We must persevere if we want to succeed in this research; too many lives are in our hands.
Sources/ references:
Bryce, Heidi. “My Story about MND and How It Has Effected My Life.” Home,
effected-my-life.
Chaytow, Helena, et al. “The Role of Survival Motor Neuron Protein (SMN) in Protein
Homeostasis.” Cellular and Molecular Life Sciences : CMLS, Springer International
Publishing, Nov. 2018, www.ncbi.nlm.nih.gov/pmc/articles/PMC6182345/.
INSERM US14 -- ALL RIGHTS RESERVED. Orphanet: Proximal Spinal Muscular Atrophy Type
1, www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=83330.
“Motor Neuron Disease.” Motor Neuron Disease | American Association of Neuromuscular &
Electrodiagnostic Medicine, www.aanem.org/Patients/Muscle-and-Nerve-
Disease#:~:text=Who%20gets%20Motor%20Neuron%20Disease,will%20get%20motor%
20neuron%20dIsease.
“Motor Neuron Diseases Fact Sheet.” National Institute of Neurological Disorders and
Stroke, U.S. Department of Health and Human Services,
ron-Diseases-Fact-Sheet.
“Motor Neuron Diseases Information Page.” National Institute of Neurological Disorders
and Stroke, U.S. Department of Health and Human Services,
www.ninds.nih.gov/Disorders/All-Disorders/Motor-Neuron-Diseases-Information-Page.
“Neurodegenerative Diseases .” MedlinePlus, U.S. National Library of Medicine, 14 July
2020, medlineplus.gov/degenerativenervediseases.html.
“What?” JPND,
ive%20diseases%20include,or%20death%20of%20nerve%20cells.
Comments