Motor Neurone Disease

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Introduction

Introduction

Motor neurone disease is a rare condition that progressively damages parts of the nervous system. This leads to muscle weakness, often with visible wasting.

Motor neurone disease, also known as amyotrophic lateral sclerosis (ALS), occurs when specialist nerve cells in the brain and spinal cord called motor neurones stop working properly. This is known as neurodegeneration.

Motor neurones control important muscle activity, such as:

  • gripping
  • walking
  • speaking
  • swallowing
  • breathing

As the condition progresses, people with motor neurone disease will find some or all of these activities increasingly difficult. Eventually, they may become impossible.

It's not clear what causes motor neurones to stop working properly. In about 5% of cases there's a family history of either motor neurone disease or a related condition called frontotemporal dementia. This is known as familial motor neurone disease. In most of these cases, faulty genes have been identified as making a major contribution to the development of the condition.

There's no single test to diagnose motor neurone disease and diagnosis is based mainly on the opinion of a brain and nervous system specialist (a neurologist). The diagnosis of motor neurone disease is usually clear to an experienced neurologist, but sometimes specialised tests are needed to rule out other conditions with similar features.

Read more about the causes of motor neurone disease and diagnosing motor neurone disease.

Progression of symptoms

The symptoms of motor neurone disease begin gradually over weeks and months, usually on one side of the body initially, and get progressively worse. Common early symptoms include:

  • a weakened grip, which can cause difficulty picking up or holding objects
  • weakness at the shoulder that makes lifting the arm difficult
  • a "foot drop" caused by weak ankle muscles
  • dragging of the leg
  • slurred speech (dysarthria)

The condition isn't usually painful.

As damage progresses, symptoms spread to other parts of the body and the condition becomes more debilitating.

Eventually, a person with motor neurone disease may be unable to move. Communicating, swallowing and breathing may also become very difficult.

In up to 15% of cases, motor neurone disease is associated with a type of dementia that can affect personality and behaviour. This is called frontotemporal dementia, and is often an early feature when it occurs in motor neurone disease. The affected person may not realise that their personality or behaviour is different.

Who's affected by motor neurone disease?

Motor neurone disease is a rare condition that affects around two in every 100,000 people in the UK each year. There are about 5,000 people living with the condition in the UK at any one time.

The condition can affect adults of all ages, including teenagers, although this is extremely rare. It's usually diagnosed in people over 40, but most people with the condition first develop symptoms in their 60s. It affects slightly more men than women.

Treating motor neurone disease

There's currently no cure for motor neurone disease. Treatment aims to:

  • make the person feel comfortable and have the best quality of life possible
  • compensate for the progressive loss of bodily functions such as mobility, communication, swallowing and breathing

For example, a breathing mask can greatly help the symptoms of breathing and weakness, and a feeding tube (called a gastrostomy) helps maintain nutrition and overall comfort. If necessary, medication can be used to help control excessive drooling.

A medication called riluzole has shown a very small improvement in patients' overall survival, but it isn't a cure and doesn't stop the condition progressing.

Read more about treating motor neurone disease.

Survival rates

Motor neurone disease is a severely life-shortening condition for most people. Life expectancy for about half of those with the condition is three years from the start of symptoms. However, some people may live for up to 10 years, and in rarer circumstances even longer.

Living with motor neurone disease is extremely challenging and often a terrifying possibility before the diagnosis is made. However, it's not necessarily as bleak as people imagine.

With strong community and specialist support, many people can maintain some independence for a significant part of the condition's course, and experience a quality of life they may not have imagined was possible at the time of their diagnosis.

The end of life for someone with motor neurone disease isn't usually distressing and is most often in their own home. In most cases, a person with the condition will die in their sleep as the end stage of gradual weakness in their breathing muscles. Although some people with the condition will have swallowing problems, they won't choke to death.

Advice and support

The Motor Neurone Disease Association (MNDA) is the leading UK charity for people affected by the condition.

The MNDA can give you information, practical advice and support about living with motor neurone disease and coping with the emotional impact of being diagnosed.

The MNDA also run a network of specialist hospital clinics across the UK, where a neurologist who's an expert in motor neurone disease can provide you with further information and advice.

Information about you

If you have motor neurone disease, your clinical team will pass information about you on to the National Congenital Anomaly and Rare Diseases Registration Service (NCARDRS).

This helps scientists look for better ways to prevent and treat this condition. You can opt out of the register at any time.

Find out more about the register.


Symptoms of motor neurone disease

Symptoms of motor neurone disease

The initial symptoms of motor neurone disease often affect certain areas of the body before eventually becoming more widespread.

It's important to visit your GP as soon as possible if you have the typical early symptoms of motor neurone disease. There's evidence that specialist care can improve overall survival.

The symptoms usually follow a pattern that falls into three stages:

  • the initial stage
  • the advanced stage
  • the end stage

Initial symptoms

The initial symptoms of motor neurone disease usually develop slowly and subtly over time. It can be easy to mistake early symptoms for those of several unrelated conditions that affect the nervous system.

Limb-onset disease

In about two-thirds of people with motor neurone disease, the first symptoms occur in the arm or leg. This is sometimes called limb-onset disease. These symptoms include:

  • a weakened grip, which can cause difficulties picking up or holding objects
  • weakness at the shoulder, making lifting the arm above the head difficult
  • tripping up over a foot because of weakness at the ankle or hip

These symptoms are usually painless and may be accompanied by widespread twitching of the muscles (fasciculations) or muscle cramps, and there may be visible wasting of the muscles with significant weight loss.

Bulbar-onset disease

In a quarter of cases, problems initially affect the muscles used for speech and swallowing. Increasingly slurred speech (dysarthria) is usually the first sign of this type of motor neurone disease, and may be misdiagnosed as a stroke.

As the condition progresses, it may become increasingly difficult to swallow (dysphagia), and be misdiagnosed as a blockage in the throat.

Respiratory-onset disease

In extremely rare cases, motor neurone disease starts by affecting the lungs, rather than affecting them at the end of the condition. This is called respiratory-onset disease.

In some cases the initial symptoms are obvious, such as breathing difficulties and shortness of breath.

In other cases the symptoms are less noticeable, such as waking up frequently during the night because the brain is temporarily starved of oxygen when lying down. This can make the person feel very tired and unrefreshed the next morning, sometimes with a headache.

Advanced symptoms

As motor neurone disease becomes more advanced, the differences between the various types of disease are less noticeable as more parts and functions of the body are affected. The rate at which the condition spreads varies, but generally remains the same for an individual (that is, it doesn't speed up, but doesn't slow down either).

Muscular symptoms

The limbs become gradually weaker and the muscles in the limbs may appear progressively wasted. As a result, the person will find it increasingly difficult to move the affected limbs.

The muscles may also become stiff. This is known as spasticity. Both muscle wasting and stiffness can also cause joint aches and pains.

Speaking and swallowing difficulties

At least two-thirds of people with motor neurone disease find that speaking and swallowing become increasingly difficult as the condition progresses. However, although choking episodes can be distressing they aren't the cause of death.

Saliva problems

Reduced swallowing can cause an excess of saliva, sometimes with drooling. Thicker saliva may sometimes be difficult to clear from the chest or throat due to weakening of the muscles that control coughing.

Excessive yawning

Some people with motor neurone disease have episodes of uncontrollable, excessive yawning, even when they're not tired. This can sometimes cause jaw pain.

Emotional changes

Motor neurone disease can lead to changes in a person's ability to control their emotions, particularly when there's weakness in the muscles that control speech and swallowing.

One of the most common signs is when a person has episodes of sudden uncontrollable crying or, more rarely, laughter. Doctors may call this emotional lability or emotionality.

Changes to mental abilities

Occasionally, people with motor neurone disease may have significant difficulties with concentration, planning and use of language. This is known as cognitive change and overlaps with a condition called frontotemporal dementia.

The changes are usually quite subtle, making it difficult to tell them apart from the normal ageing process, and they don't normally affect a person's capacity to make their own decisions.

Up to 15% of people with motor neurone disease develop more profound frontotemporal dementia, usually soon after, or sometimes before, their first muscle-related symptoms. The affected person may not be aware that there are problems with their behaviour or personality.

Breathing difficulties

As the nerves and muscles that help control the lungs become progressively more damaged, the person's breathing will become less efficient.

This may be a feeling of being very short of breath after doing everyday tasks, such as walking up the stairs. However, over time, the person may even become short of breath when they're resting.

Shortness of breath may be particularly troublesome at night. Some people find it difficult to breathe when they're lying down. Others may wake up in the night because of breathlessness.

As motor neurone disease progresses, a non-invasive breathing mask may be recommended at night to improve sleep quality and help reduce drowsiness during the day.

End-stage symptoms

As motor neurone disease progresses to its final phase, a person with the condition will probably experience:

  • increasing body paralysis, which means they'll need help with most daily activities
  • significant shortness of breath

Eventually, non-invasive breathing assistance won't be enough to compensate for the loss of normal lung function. At this stage, most people with motor neurone disease become increasingly drowsy before falling into a deep sleep, where they usually die peacefully.

Secondary symptoms

Some people with motor neurone disease have additional symptoms that aren't directly caused by the condition but are related to the stress of living with it. These may include depressioninsomnia and anxiety.

Although many people with motor neuron disease may think about ending their life at some point, this isn't a common outcome, particularly with strong family and community support.

Causes of motor neurone disease

Causes of motor neurone disease

Motor neurone disease occurs when specialist nerve cells (motor neurones) in the brain and spinal cord progressively lose their function. It's not clear why this happens.

In most cases, a person with motor neurone disease won't have a family history of the condition. This is known as sporadic motor neurone disease. Researchers believe that the cause is probably a series of steps involving a mixture of damaging genetic and environmental factors. As we get older, we may gradually lose the ability to keep this damage under control, triggering irreversible neurodegeneration.

About 5% of people with motor neurone disease have a close family relative with the condition or a related condition known as frontotemporal dementia. This is called familial motor neurone disease which can be hereditary or linked to a problem with genes that can cause problems at a younger age.

Possible causes of motor neurone disease

It's still unclear why the motor neurones begin to lose function. Most experts believe that it's a combination of interrelated factors that ultimately affect either the motor neurones or the nerve cells that support them.

Aggregates and RNA processing

Aggregates are abnormal clumps of protein that develop inside motor neurones. They are found in nearly all cases of motor neurone disease and may disrupt the normal working of the motor neurones, or at least be a marker that the cell is under great strain.

The most common aggregate found is TDP-43, which is a very important protein involved in the correct processing of the genetic instructions for the cell through a molecule known as RNA.

Cell transport disruption

All cells contain transport systems that move nutrients and other chemicals into the cell and waste products out of the cell. Research suggests that the transport systems in motor neurones become disrupted. Over time, toxic waste can build up in cells as a natural by-product of normal cell activity.

The body gets rid of the toxic waste by producing substances known as antioxidants, and packaging the waste into containers called microvesicles. Research suggests that in motor neurone disease the motor neurones may be deficient in antioxidants. However, there's no evidence that this is due to poor dietary intake.

Glial cells

Glia are cells that surround and support motor neurones and provide them with nutrients. Glial cells also help relay information from one nerve cell to another.
Some cases of motor neurone disease may be caused by problems with the glial cells, which means that the motor neurones no longer receive the support and nutrition they need to function normally.

Glutamate

Nerve cells use special "messenger chemicals" called neurotransmitters to pass information from one cell to another. One of the neurotransmitters is called glutamate. There's evidence that the motor neurones in people with motor neurone disease may have become more sensitive to glutamate, resulting in damage to these cells. However, this isn't linked to dietary intake of glutamate.

Mitochondria

Mitochondria are the "batteries" of cells. They provide the energy that a cell needs to carry out its normal function. Research has shown that the mitochondria in the motor neurones of people with motor neurone disease seem to become abnormal.

Familial motor neurone disease

The fact that motor neurone disease can run in families suggests that single genetic mutations inherited from parents may sometimes have a much larger role in the condition.

A genetic mutation occurs when the instructions carried in cells become scrambled in some way. This results in one or more of the body's processes not working properly. Read more about genetics.

Four major genetic mutations have so far been identified in the 5% of people with a family history of motor neurone disease or the related condition, frontotemporal dementia.

The largest group (about one third) have an expanded area of a gene called C9ORF72. Some people with this gene abnormality develop motor neurone disease, some develop frontotemporal dementia and some develop both. Other genes linked to familial motor neurone disease include SOD1, TARDBP and FUS.

If your father, mother, sister or brother developed motor neurone disease and were found to have one of these abnormal genes, you have a 50% chance of carrying the same gene. However, importantly, this doesn't necessarily mean you'll definitely develop motor neurone disease in your lifetime.

If you've been diagnosed with motor neurone disease but there's no wider family history, the overall risk to your own children is currently thought to be similar to that of the general population.

Genetic testing is available to determine whether you have one of the mutated genes associated with familial motor neurone disease. Your GP can give you more information about appropriate specialists who can help with the complex issue of when to perform genetic testing.


Diagnosing motor neurone disease

Diagnosing motor neurone disease

See your GP if you experience the initial symptoms of motor neurone disease, such as a progressive, usually painless, weakness of grip.

After an initial examination, they may refer you to a brain and nervous system specialist (a neurologist) for a further opinion and possibly tests.

Diagnosing motor neurone disease can be difficult during the condition's initial stages because many of the early symptoms can be caused by other more common health conditions such as:

  • a trapped nerve - wear and tear of the bones in the spine can sometimes cause nerves to become trapped and compressed under the spine
  • peripheral neuropathy - where part of the nervous system becomes damaged by another health condition, most commonly type 2 diabetes

Initial testing

Motor neurone disease is usually diagnosed by a neurologist based on the symptoms and a physical examination.

There's no single test for motor neurone disease, but the diagnosis is often obvious from a person's symptoms and physical examination by a neurologist. Various tests may be used to rule out other possible causes of the person's symptoms if they seem likely. Tests may include:

  • blood tests - these can be used for several reasons, such as checking that certain organs, such as your thyroid, are working normally, or to look for a marker of muscle weakness (creatinine kinase)
  • magnetic resonance imaging (MRI) scan - to give a detailed image of the inside of your brain and spinal cord
  • electromyography (EMG) - measures the electrical activity in your muscles, which shows how well your motor neurones are working and connecting to the muscles
  • nerve conduction test - similar to an EMG but measures how quickly your nerves can conduct an electrical signal
  • lumbar puncture - a sample of spinal fluid may be removed for testing to exclude an inflammatory nerve condition 
  • muscle biopsy - in rare cases, a small sample of muscle may be removed for testing to determine whether the problem lies in the muscles or nerves

Confirming the diagnosis

There are many reasons why there may be delays in diagnosis. It may be that the initial symptoms aren't thought to be serious, or they're not recognised as being related to the nervous system so a neurologist isn't initially consulted.

Sometimes, the diagnosis of motor neurone disease is clear without the need for further tests. However, confirming a diagnosis can sometimes be time-consuming even for an experienced neurologist, who occasionally needs a period of observation to be sure, particularly in cases where the condition progresses slowly. Motor neurone disease can only be diagnosed if the symptoms are clearly getting worse (progressive).

Receiving the diagnosis

Being told you have motor neurone disease can be emotionally devastating and the news can be difficult to take in at first. Many people diagnosed with the condition go through the classic stages of the grieving process. These are:

  • denial - you may initially disbelieve the diagnosis and think there's nothing wrong with you or that your doctor has missed another diagnosis
  • anger - you may feel angry towards friends, family or medical staff, particularly if you feel that the diagnosis has been unduly delayed
  • bargaining - people with terminal conditions sometimes try to "bargain" with their doctors, asking for any sort of treatment that can prolong their life
  • depression - you may lose interest in life and feel that your situation is hopeless
  • acceptance - you come to terms with the diagnosis, the feelings of depression pass, and you begin to plan the rest of your life

If you've been diagnosed with motor neurone disease, talking to a counsellor or a trained clinical psychologist may help combat feelings of depression and anxiety.

It's not unusual to have thoughts of taking your own life, although very few people with motor neurone disease go on to do this. You shouldn't be concerned about discussing any such thoughts with your doctor. 

Taking antidepressants or medicines to reduce anxiety may also help as you move through the stages of the grieving process. Your care team will be able to advise you about this.


Treating motor neurone disease

Treating motor neurone disease

There's no cure for motor neurone disease, but treatment can help relieve symptoms and help to slow down the condition's progression.

Your care team

If you're diagnosed with motor neurone disease, you'll be introduced to a team of healthcare professionals who'll be involved in your care. This team is often called a multidisciplinary team and typically includes a neurologist (or palliative care physician) and a specialist nurse.

Advance decision

An important principle of medical care is that patients feel in charge of what is, and what isn't, done to them. Many people with motor neurone disease draw up an advance decision (sometimes called an advanced directive). This is where you make your treatment preferences known in advance in case you can't communicate your decisions later because you're too ill.

Issues that can be covered by an advance decision include:

  • whether you want to be treated at home, in a hospice or in a hospital once you reach the final stages of motor neurone disease
  • the type of medication you'd be willing to take in certain circumstances
  • whether you'd be willing to consider a feeding tube if you were no longer able to swallow food and liquid
  • if you have respiratory failure (loss of lung function) in the latter stages of motor neurone disease, whether you wish to be resuscitated by artificial means, such as having a permanent breathing tube inserted into your throat (known as a tracheostomy)
  • whether you'd be willing to donate any of your organs after you die (the brain and spinal cord of people with motor neurone disease are very important for ongoing research)

Your care team will be able to provide you with more information and advice about making an advance decision.

Read more about end of life care.

Riluzole

Riluzole is the only medication that's shown a survival benefit for people with motor neurone disease. Riluzole is thought to slow down the progressive damage to the motor neurone cells by reducing their sensitivity to the nerve transmitter glutamate.

In medical research, riluzole extended survival by two to three months on average, although this varied from person to person and the condition continued to progress even with riluzole treatment.

Side effects of riluzole are usually mild and commonly include nausea, tiredness and, less commonly, a rapid heartbeat.

Very rarely, riluzole has been known to cause liver damage. If you're prescribed riluzole you'll need to have blood tests for the first few months to check your liver is working properly. If you've had significant liver disease, riluzole may not be suitable for you.

Treating symptoms

A range of treatments can relieve many of the symptoms of motor neurone disease and improve your quality of life.

Muscle cramps

Muscle cramps can be helped by physiotherapy and, in some cases, a medication called quinine. They typically improve later in the condition.

Quinine can cause side effects, such as:

  • hearing and vision problems
  • tinnitus - the perception of noise in one ear, both ears or inside the head
  • vertigo - a sensation that you, or the environment around you, is moving  

Because of this, quinine will usually only be used if the potential benefits are thought to outweigh the risks.

Muscle stiffness

Muscle stiffness, also known as spasticity, can be treated using medication such as baclofen to help relax the muscles. Side effects may include increased weakness or tiredness.

Drooling

Drooling of watery saliva can be treated with a number of medications. One widely used medication is a hyoscine hydrobromide skin patch. It was originally designed to treat motion sickness, but has since proved useful in drying up the flow of saliva.

Amitriptyline, atropine eye drops applied to the tongue, glycopyrrolate, or botulinum toxin injections are alternative medicines that can also be used to control drooling.

Communication difficulties

Not everyone with motor neurone disease will have significant speech problems, but there's a lot of help for people who do. A speech and language therapist can teach you several techniques to make your voice as clear as possible.

As motor neurone disease progresses, you may need assistive technology to help you communicate. A range of communication aids is available. Your therapist will be able to advise you about the most effective communication aids for you.

Swallowing difficulties

Not everyone with motor neurone disease will have significant swallowing problems (dysphagia). For those that do, it can prevent normal eating and drinking. If food goes down the wrong way into the lungs it can cause chest infections (called aspiration). Weight loss due to poor nutrition can also accelerate motor neurone disease.

One widely used treatment for dysphagia is a thin feeding tube known as a percutaneous endoscopic gastrostomy (PEG) tube. The tube is surgically implanted into your stomach through a small cut on the surface of the stomach. It shouldn't restrict your daily activities and you can continue to bathe and swim normally if you wish. It's advisable to have the tube inserted before the breathing muscles are significantly weakened, even if it isn't used for feeding until sometime later.

Pain relief

Motor neurone disease isn't usually a painful condition. If you experience pain, it's often aching joints caused by muscle weakness or a change in posture. The type of painkiller recommended will depend on how severe the pain is.

Mild to moderate pain can often be controlled using non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen. More severe pain is very rare, but it can be treated using an opiate-based painkiller such as morphine.

In some cases, a type of medication called gabapentin is used. It was originally designed to treat epilepsy but it's also useful for treating pain. Drowsiness is a typical side effect of gabapentin.

Breathing difficulties

As motor neurone disease progresses, the muscles that help you breathe will become weaker and your breathing will become increasingly shallow, with a weaker cough.

Breathing difficulties usually develop gradually, although rarely they may be the first sign of motor neurone disease.

It's important to discuss breathing problems with your GP before they occur. Your GP or neurologist should be able to refer you to a respiratory specialist or a palliative care specialist, as appropriate.

Many people with motor neurone disease benefit from non-invasive mechanical ventilation (NIV) to support their breathing, usually overnight when asleep. Room air (not oxygen) is sucked into a small box, filtered and then gently pumped into the lungs through a face mask or nasal tube each time the person takes a breath.

NIV may not be suitable for everyone with motor neurone disease. Your respiratory or palliative care specialist will be able to discuss the options available to you.

Deciding what treatment you want to use in the event of respiratory failure is an important part of drawing up a treatment plan and making an advance decision. This can be a very difficult and upsetting decision, and you may want to discuss it with your loved ones.

Your care team can also give you information and advice but the final decision will be yours.

Complementary therapies

Some people with motor neurone disease find complementary therapy helpful. This involves combining conventional treatments with non-medical treatments, such as acupuncture.

Complementary therapies can't slow the progression of motor neurone disease, but they may help reduce stress and make your daily life more comfortable.

Before considering complementary therapy, you should seek advice from your treatment team and ensure that any practitioners you contact are appropriately registered, qualified and experienced.

Advice for carers

Caring for someone with motor neurone disease can be both physically and emotionally demanding, and it's likely you'll need a wide range of support.

See the practical guide to caring for information and advice about all aspects of caring.