Motor Neuron Disease (MND)

A motor neuron disease (MND) is any of five neurological disorders that selectively affect motor neurons, the cells that control voluntary muscle activity including speaking, walking, swallowing, and general movement of the body. They are neurodegenerative in nature, and cause increasing disability and, eventually, death

Classification/Types

In the most common classification, the term "motor neuron disease" applies to the following five disorders which affect either upper motor neurons (UMN) or lower motor neurons (LMN), or both:

1.       ALS (amyotrophic lateral sclerosis) is the most common form and accounts for approximately 60% to 70% of all cases.

2.       PLS (primary lateral sclerosis) is a very rare form of MND. PLS, unlike the other forms, is not fatal. In some very rare cases, patients with PLS eventually have ALS.

3.       PBP (progressive bulbar palsy) accounts for about 20% of all cases.

4.       PMA (progressive muscular atrophy) accounts for the remaining 10% of cases.

In all three MND forms symptoms are very similar. However, they progress at different speeds.

 Risk factors

A risk factor is something that increases a person's chances of developing a disease. For example, smoking increases the risk of developing some types of cancer; therefore, smoking is a risk factor for cancer.

1.       Heredity - approximately 1 in every 10 people with ALS in the USA are known to have inherited it from their parents. A child who has a parent with MND has a 50% chance of developing the disease.

2.       Age - after the age of 40 the risk of developing MND rises significantly (but is still very small).

3.       Sex - men are much more likely to develop the disease before the age of 65 than women. After 70 years of age the risk is the same for both sexes.

4.       Where you live - incidence of MND is significantly higher in parts of Japan, West New Guinea and Guam, compared to other parts of the world (even so, the risk is still small in those areas).

5.       Military experience - some studies have suggested that people who are or have been in the military (army, navy, air force, marines) have a higher chance of developing the disease than other people.

6.       Professional football - professional football players have a much higher risk of dying from ALS, Alzheimer's diseases, and other neurodegenerative diseases, scientists from the National Institute for Occupational Safety and Health in Cincinnati explained in Neurology. (The American word "football" refers to the British word "American football)

Some other features they may also help to progress the MND:

a.       Smoking

b.      Head injuries, especially repeated ones

c.       Exposure to pesticides

d.      A diet that is very high in fat

e.      Exposure to some chemicals, such as formaldehyde

Clinical Presentation of MND

In most cases of MND, symptoms follow a pattern depending on which of the three stages the patient is in. MND is divided into three stages - the initial stage, the advanced stage and the end stage.

A. During the initial stage
At this stage symptoms develop slowly and faintly. Symptoms include:

a.       The patient's grip weakens. Sometimes picking up and/or holding things can be difficult.

b.      Fatigue

c.       Muscular pains, cramps & twitches

d.      Slurred and sometimes garbled speech

e.      Weakness in the limbs

f.        Increased clumsiness

B. During the advanced stage

a)      Muscle weakness and pain.

b)      Limbs become progressively weaker and muscles start to shrink.

c)       Movement in affected limbs becomes progressively more difficult.

d)      Muscle spasms and twinges get worse.

e)      Some limb muscles become abnormally stiff (spasticity).

f)       Pain in joints.

g)      Progressive dysphagia - swallowing difficulties which get worse with time, making eating and drinking harder to do.

h)      Drooling - this is often due to problems controlling saliva production.

i)        Yawning - sometimes yawning can come in uncontrollable bouts.

j)        Jaw pain - often caused by excessive yawning.

k)      Speech problems - as muscles of the throat and mouth become weaker the patient has speech problems, making communication harder.

l)        Change in personality and emotional state - often a patient at this stage experiences emotional liability (bouts of uncontrollable crying or laughing).

m)    Memory and some cognitive changes - some patients experience changes in their ability to remember things and learn new things. Language ability and concentration span may also be affected. If the patient is elderly it may be hard to know whether this is being caused by age or the disease.

n)      Dementia - a small proportion of MND patients are diagnosed with dementia.

o)      Breathing problems - progressive damage to muscles that control the lungs eventually result in breathing difficulties. The patient may feel short of breath after what hitherto had been thought of as a normal task.

C. During the end stage

               i.            Typically, the patient's body will eventually become totally paralyzed.

             ii.            Breathing difficulties worsen and become serious. An oxygen mask will not be enough. As the problem worsens the patient becomes increasingly drowsy, and eventually falls into a deep sleep and dies peacefully.

D. Secondary symptoms
Secondary symptoms include:

a.       Insomnia

b.      Depression

c.       Anxiety

Causes

MND happens when motor neurons lose their function gradually and progressively. Motor neurons are neurons that send electrical output signals to muscle neurons, also called motoneurons. Motor neurons are found in the brain and spine. When motor neurons relay signals from the brain to the muscles and bones, the muscles move. Motor neurons are also involved in many of our automatic movements, such as swallowing and breathing.
Scientists are not sure why motor neurons start to lose function. They believe several inter-related factors cause MND, including:

1.       Excess glutamate - glutamate is a neurotransmitter, a messenger chemical that transmits data from cell-to-cell. Some studies indicate that people with MND have too much glutamate. Abnormally high levels of glutamate may be toxic and could lead to a disturbance in the chemical communication required for good nerve function.

2.       Cell metabolism - transport systems exist in all cells that bring nutrients and chemical components into the cell, while at the same time moving waste products out. Scientists say there are indications that these transport systems are disturbed in the motor neurons during the initial stages of MND., resulting in poor nerve function.

3.       Lack of antioxidant production - research indicates that the motor neurons of patients with MND do not produce enough antioxidants to neutralize the free radicals that emerge as a natural by-product of cell activity. Oxygen free radicals are a type of toxic waste cells produce - antioxidants mop them up.

4.       Mitochondria of motor neurons - research has found that the mitochondria of motor neuron cells of people with MND appear to be abnormal. Mitochondria provide the energy cells need to carry out their normal function - they are normal structures responsible for energy production in cells.

5.       Neurotrophic factors - these are molecules, usually proteins that facilitate the growth or repair of nerve cells. It has been found that neurotrophic factors are not produced properly in patients with MND, making the motor neurons more susceptible to damage.

6.       Glia cells - these cells surround neurons and provide support for them and insulation between them. They also provide motor neurons with nutrients and relay data from one cell to another. In some cases, problems with glia cells can affect the motor neurons.

Diagnosis

During its initial stage MND may be difficult to diagnose because the signs and symptoms are commonly found in other diseases and conditions, such as MS (multiple sclerosis), trapped nerve, or Parkinson's disease.

Blood and urine tests: Creatinine kinase; creatinine kinase is produced when muscle breaks down.

MRI (magnetic resonance imaging) scan - An MRI scan will not diagnose MND - damage caused by MND does not show up on an MRI. However, it is a useful test in ruling out damage caused by other conditions and diseases which do show up, such as stroke, Alzheimer's disease, Parkinson's disease, and others.

An EMG (electromyography) - Most patients find this test mildly uncomfortable. Muscles which have lost their nerve supply can be identified because their electrical activity is different from healthy muscle. The EMG may appear as abnormal even if that particular muscle is not yet affected.

A nerve conduction test - measures how fast the nerves can conduct an electrical impulse. Electrodes are attached to the skin above the nerve or muscle that is being studied. A small electric shock is passed through the nerve to measure the strength and velocity of the nerve signals.

TMS (transcranial magnetic stimulation) - the activity of the upper motor neurons is measured using a specially designed magnetic coil. This procedure may be carried out at the same time as a nerve conduction test.

Muscle biopsy – If the patient may have a muscle disease, rather than MND, a muscle biopsy may be performed. A small portion of muscle is removed. The patient receives a local anesthetic beforehand. The muscle sample is sent to the laboratory for analysis.

Treatment

As there is no way of reversing the progression of motor neuron disease, treatments focus on making the patient more independent and comfortable, as well as slowing down the progression. In most countries, when a patient is diagnosed they will be introduced to a team of health care professionals - a multi-disciplinary team - who will be actively involved in their care.

The treatment for MND is the supportive care to patient for symptomatic treatment. There is no any specific treatment but one medicine that are using to treat the case of MND is

 Riluzole
This is the only drug specifically targeted for MND patients. Riluzole appears to lower the amount of glutamate in the body, resulting in slower progression of the disease. Not only does Riluzole lengthen a patient's lifespan, it also delays the onset of ventilator-dependence or tracheotomy in selected patients. 

References:

1.       MNT

2.       NHS choice

3.       Wikipedia