Types of Motor Neuron Disease and Their Causes

What is Motor Neuron Disease?

Motor Neuron Disease (MND) is the umbrella term used for a group of neurodegenerative conditions, which lead to the progressive deterioration of the voluntary muscles of the body. Motor neurons are nerves which innervate muscles, sending instructional signals to control them. Upper motor neurons (UMNs) found in the brain transmit their signals to the lower motor neurons (LMNs) in the spinal cord, which go on to stimulate the muscles of the body. In MND, these specific neurons degenerate and die, depriving muscles of nervous signals. Without signals from the brain these muscles waste away, impairing motor function.

What are the different types of MND?

There are several different variants of MND. They all share the fundamental principle of motor neuron degeneration; however, they vary in their range and degree of symptoms, as well as disease progression. Every individual experiences the disease differently; some present with all the symptoms, while others experience only a few.

The pattern and location of motor neuron deterioration is used to classify the disease into four main types. As the disease progresses, patients often develop degeneration of both the UMNs and LMNs, though only one type may have been affected to begin with.

Amyotrophic lateral sclerosis (ALS)

ALS or Lou Gehrig's disease is the most common form of the disease and makes up 80-90% of cases. Both UMNs and LMNs are affected, leading to loss of control of the voluntary muscles. Initially, the patient presents with symptoms of limb muscle weakness, stiffness, and spasms. Individuals increasingly trip while walking, or drop things.  As the disease progresses, other muscles deteriorate, such as those for speech, swallowing, and breathing. Patients also experience unstable and rapidly changing emotions.

From the onset of symptoms, the life expectancy for ALS is between 2-5 years. Patients typically die as a result of failure of the respiratory muscles. Around 10% of individuals with ALS survive for more than 10 years, as seen with the late theoretical physicist, Stephen Hawking, who lived on for another 55 years.

Progressive bulbar palsy (PBP)

PBP affects 4.1% of individuals with MND. This variant affects the motor neurons in the bulbar region of the brain, leading to weakness of the muscles of the face and neck. Symptoms include difficulties in chewing, swallowing, speech and neck extension; limbs are usually affected later as the disease progresses. This rapidly progressing variant of MND leads to a shorter life expectancy of 6 months to 3 years.

Progressive muscular atrophy (PMA)

LMNs are mainly targeted in this rare disorder, however, variable UMN deterioration occurs in some individuals, often increasing as the disease advances. Isolated LMN deterioration is only observed in 15% of patients, while 85% show some deterioration of both UMNs and LMNs. Due to this overlap, patients with PMA are often misdiagnosed as having ALS.

Early symptoms are usually localized to the hand or leg for a number of years before progressing to the rest of the body. These include clumsiness, weakness and fasciculation (twitching) of the muscles. Symptoms later advance to respiratory failure, similar to ALS. However, the progression of the disease is slower than in other types, allowing for longer survival post-diagnosis of 5-7 years.

Primary lateral sclerosis (PLS)

This rare disease targets the upper motor neurons exclusively. It leads to weakness, stiffness and spasticity in the lower limbs, which progresses to the trunk, arms, hands, tongue and jaw. At an advanced stage of the disease, some individuals develop  speech impairments and difficulty with breathing or swallowing. Those with adult PLS do not have a reduced life expectancy as the disease is not fatal, but it may be quite debilitating and reduce their quality of life.

What causes MND?

There is no identifiable cause for MND. 10% of cases are familial, which means individuals have inherited a faulty copy of a gene. The SOD gene, which encodes an antioxidant, has been shown to be mutated in familial MND, leading to free radical toxicity affecting MNs.

Most cases of MND are sporadic, meaning they occur randomly without a known cause. Ongoing research has suggested several causes which include:

• Toxins
• Environmental chemicals
• Viral infections
• Intense physical activity
• Loss of growth factors to developing motor neurons
• Mitochondrial dysfunction
• Oxidative injury to neurons
• Excessive excitability of neurons

The evidence is conflicting, and no definitive causes have been established. It is therefore not possible to provide the public with advice on how to prevent the disease.

Further Reading

• All Motor Neurone Disease Content
• What is Motor Neurone Disease?
• Motor Neurone Disease Causes
• Motor Neurone Disease Diagnosis
• Motor Neurone Disease Symptoms

Written by

Stephanie Hunter

Stephanie obtained a first-class honors degree in Biomedical Science from the University of Sheffield in 2017. The modules she studied included: cell biology, membrane receptors, stem cells, tissue engineering, cancer, physiology, anatomy, and pharmacology. During her final year, she wrote a literature review on ‘Cell Therapy in Curing Muscular Dystrophy’, in which she analyzed different cell types with different genetic manipulations for their potential use in cell therapy.