What Is Motor Neuron Disease? What Is Amyotrophic Lateral Sclerosis (ALS), Or Lou Gehrig's Disease?

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Main Category: Muscular Dystrophy / ALS
Also Included In: Neurology / Neuroscience
Article Date: 17 Sep 2009 - 9:00 PDT

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Motor neuron disease (MND) is a serious and incurable form of progressive neurodegeneration - over time the nerves in the spine and brain progressively lose function. In the case of motor neuron disease, motor neurons - types of nerve cells - are affected.

The renowned English physicist, Stephen Hawking, and guitar virtuoso Jason Becker are living with motor neuron disease.

There are different forms of motor neuron disease

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


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


• 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.

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.

A rare disease

MND is a very rare condition that affects the nervous system (neurological condition). In the UK approximately 1 person in every 50,000 is diagnosed with MND each year.

MND can affect patients of any age, but most of them develop the disease and are affected by it after the age of 40 (specifically between the ages of 50 and 70 years). Out of every 10 people with AMD 6 are men and 4 are women.

What are the risk factors for motor neuron disease?

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.

• 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.


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


• 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.


• 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).


• 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.

The following risk factors have also been suggested:

• Smoking
• Head injuries, especially repeated ones
• Exposure to pesticides
• A diet that is very high in fat
• Exposure to some chemicals, such as formaldehyde

What are the symptoms of motor neuron disease?

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.

MND signs and symptoms during the initial stage

At this stage symptoms develop slowly and faintly. Patients are likely to mistake some of the early symptoms for some other unrelated neurological condition. Symptoms include:

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


• Fatigue


• Muscle pains


• Muscle cramps


• Muscle twitches


• Slurred and sometimes garbled speech


• Weakness in the limbs


• Increased clumsiness

MND signs and symptoms during the advanced stage

• Muscle weakness.


• Limbs become progressively weaker.


• Limb muscles start to shrink.


• Movement in affected limbs becomes progressively more difficult.


• Muscle spasms and twinges get worse.


• Some limb muscles become abnormally stiff (spasticity).


• Pain in muscles.


• Pain in joints.


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


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


• Yawning - sometimes yawning can come in uncontrollable bouts.


• Jaw pain - often caused by excessive yawning.


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


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


• 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.


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


• 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.


• Shortness of breath eventually becomes apparent even when the patient is resting. Some patients may have breathing difficulties when lying down, which can affect sleeping and sleeping patterns. Patients eventually need mechanical assistance with their breathing (e.g. an oxygen mask).

MND signs and symptoms during the end stage

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


• 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.

Secondary symptoms

These are symptoms that are not caused by the disease directly, but are linked to the mental toll of living with MND. Secondary symptoms include:

• Insomnia
• Depression
• Anxiety

What are the causes of motor neuron disease?

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:

• 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.


• 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.


• Aggregates - unusual clumps of protein molecules have been found to accumulate in the motor neurons of MND patients. Scientists believe these aggregates undermine the normal functioning of motor neurons.


• 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.


• 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.


• 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.


• 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.

How is motor neuron disease diagnosed?

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.

A GP (general practitioner, primary care physician) will refer the patient to a neurologist - a doctor specialized in the diagnosis and treatment of diseases and conditions of the nervous system. The neurologist may order the following tests:

• Blood and urine tests - by analyzing samples of the patient's blood and urine in the lab the doctor can rule out other possible causes for the signs and symptoms. A blood test can also determine whether there is any rise in creatinine kinase, which can sometimes be found in the blood of patients with MND. Creatinine kinase is not specific for MND and may also be an indicator of some other medical condition. Creatinine kinase is produced when muscle breaks down.


• An MRI (magnetic resonance imaging) scan - radio waves and a powerful magnetic field produce detailed images of the brain and spinal cord on a monitor. The patient lies on a movable bed that slides into a tube-shaped machine. When the machine is switched on and the patient is inside he/she will hear loud thumping and banging noises - this is normal. 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) - needles are used to measure the electrical activity in the patient's muscles. A fine wire electrode is inserted into the muscles that the doctor wants to study - usually muscles from each limb and the bulbar (throat). An instrument records the electrical activity or the muscle while it is resting and contracting. 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.


• Spinal tap (lumbar puncture) - the aim here is to analyze the cerebrospinal fluid; the fluid that surrounds the brain and spinal cord. Patients lie on their side with knees drawn up to the chest. A local anesthetic is injected into the area where the spinal tap occurs. A needle is then inserted into the spinal canal and some fluid is collected.


• Muscle biopsy - if the doctor thinks 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.

Before confirming a diagnosis of MND

Some neurologists may ask the patient to return a couple of months later before confirming the diagnosis, to make sure it really is MND and not something else. During the subsequent visit the doctor can see how symptoms have progressed. In many countries the neurologist uses a diagnostic checklist called the El Escorial criteria. The doctor checks for distinctive neuron signs, including:

• Muscle shrinking
• Muscle weakness
• Twitching
• Increase in muscle tone
• Alterations in normal muscle reflexes

If the neurologist finds motor neuron signs in at least three regions of the patient's body a definite MND diagnosis can be made.

Coping with a motor neuron disease diagnosis

A significant proportion of patients are emotionally devastated and shocked when they are told they have motor neuron disease. Normally, they will go through the four stages of the grieving process:

• Denial - this involves initial disbelief. The patient may try to cling on to the thought that there is nothing wrong with him/her.


• Anger - this feeling may be directed at family, friends, colleagues, health care professionals and the patient himself/herself.


• Bargaining - the patient may try to negotiate with the doctor, asking about any kind of treatment that may prolong his/her life.


• Depression - the individual may feel that everything is doomed and lose interest in life.

These feelings are normal - it is natural for a human being to go through them. In the vast majority of cases the individual eventually accepts his/her diagnosis. Many patients report that talking to a qualified counselor helped them deal with the feelings of anxiety and depression. In some cases the patient may be prescribed antidepressants or other drugs to treat the anxiety or depression.

What are the treatment options for motor neuron disease?

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. Advanced directive This is where patients express their treatment preferences in advance in case they are not able to express them adequately later on. An advanced directive may cover the following issues:

• They can state whether they want treatment to take place at home, in a hospital or hospice during the end stage of MND.


• They will list which painkillers are acceptable and which are not.


• They will state whether their organs should be donated after death, e.g. an MND patient's brain and spine could be used for research.


• They will also state what they wish to be done if specific things happen, such as respiratory failure, whether they should undergo resuscitation by artificial means (for example, whether a breathing tube may be inserted into the neck).


• In most countries today (September 2009) the patient cannot give instructions regarding assisted suicide.

Treatment to slow down neuron motor disease progression - 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.

Riluzole is marketed by sanofi-aventis with the brand name Rilutek.

About 1 in 10 patients experience side effects to such an extent that treatment has to be discontinued.

Side effects of riluzole may include:

Nausea
Vomiting
Weakness
Tachycardia (accelerated heartbeat)
Drowsiness
Headaches
Dizziness

As riluzole can sometimes cause liver damage the patient will need to have regular liver function tests. Those with a history of liver disease may not be able to have this medication.

Treatment for muscle cramps

Apart from physical therapy (UK: physiotherapy) two commonly prescribed drugs for muscle cramps associated with MND are phenotyn and carbamazepine.

Treatment for muscle stiffness (spasticity)

Muscle relaxants, or an injection of BTA (botulinum toxin) if the muscle relaxants do not work, may be prescribed by the doctor for muscle stiffness. BTA blocks the signals from the brain to the stiff muscles. An injection should be effective for about three months.

Intrathecal baclofen therapy may also help with muscle stiffness. A small pump is surgically implanted outside the body and connected to the spinal cord. A regular dose of baclofen is delivered into the nervous system. Baclofen blocks some of the nerve signals that cause spasticity. Some patients may find this treatment also helps with extreme yawning.

Treatment for drooling

Hyoscine hydrobromide, a drug for motion sickness, has also been found to help control symptoms of drooling.

Side effects of hyoscine hydrobromide include:

Drowsiness
Vision problems
Dizziness

Patients who experience any of these side effects should not drive a vehicle or operate heavy machinery.

Glycopyrrolate injection may also help with the symptoms of drooling.

Side effects of glycopyrrolate include:

Urinary problems
Arrhythmia (irregular heartbeat)
Tachycardia (accelerated heartbeat)
Vision problems

Atropine may be prescribed if hyoscine hydrobromide, or glycopyrrolate do not work. Atropine stops the saliva glands from producing saliva. Atropine may be swallowed or administered as an injection.

Side effects of atropine include:

Dry mouth
Dry skin
Urinary problems
Constipation
Heartbeat may slow down or speed up

Treatment for emotional lability

Antidepressants, called SSRIs (serotonin reuptake inhibitors) may be prescribed for episodes of uncontrollable laughter or crying (emotional lability).

Side effects of SSRIs, which improve in time, may include:

Headache
Insomnia
Nausea
Anxiety

Treatment for speech problems

Patients with MND who experience speech and communication difficulties may learn some useful techniques with a qualified SLT (speech and language therapist). As the disease advances the patient may need some communication aids.

Treatment for dysphagia (difficulties swallowing)

As MND progresses the idnvidual may eventually find it impossible to eat or drink normally. PEG (percutaneous endoscopic gastrostomy) is a surgical procedure for placing a feeding tube without needing to perform an open laparotomy (operation on the abdomen). The procedure is done in a hospital or outpatient surgical facility.

The patient receives a local anesthesia in the throat; an endoscope (flexible, light tube) then passes through the mouth, throat and esophagus to the stomach. The surgeon makes a small cut in the skin of the abdomen and pushes an intravenous cannula (an IV tube) through the skin into the stomach and ties it in place. The patient can generally go home the same day or the following morning.

Treatment for pain

An NSAID (non-steroidal anti-inflammatory drug), such as ibuprofen will help with mild to moderate pain, while morphine may be used for more severe pain.

Gabapentin, a drug used for epilepsy treatment, may sometimes be prescribed for pain associated with MND.

Side effects of gapapentin include:

Dizziness
Fatigue
Coordination problems
Drowsiness

When gabapentin is discontinued it should be done so gradually so that the patient does not suffer unpleasant withdrawal symptoms.

Treatment for breathing problems

Respiratory muscle weakness usually develops gradually, but can sometimes do so suddenly. Some patients may use mechanical ventilation to help with their breathing - the air is sucked in, filtered, and pumped into the lungs through a facemask or nasal tube.

Written by Christian Nordqvist


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