Motor neuron diseases are disorders that cause the destruction of the nerve cells that control muscle movement. They include ALS, progressive muscular atrophy (PMA), spinal muscular atrophy (SMA) and hereditary spastic paraplegia (HSP).
Symptoms appear differently in each person with MND and progress at different speeds. They depend on which type of nerve cell is affected: ALS affects both upper and lower motor neurons; PBP only lower motor neurons; SMA affects UMNs; and HSP only UMNs.
Symptoms
Motor neuron disease is an umbrella term for a group of disorders that cause the dysfunction and death of specific types of nerve cells that control movement. These cells, called motor neurons, extend from the brain to the spinal cord and then from the spinal cord to the muscles in the arms, legs and torso. They are responsible for muscle function, including speaking, swallowing and breathing. In MNDs, the degeneration of these neurons results in progressive weakness. Some of these diseases are hereditary (passed down from parents) but the majority of MNDs develop randomly and are referred to as sporadic. Mutations in certain genes have been linked to hereditary MNDs, but many other causes of the disease are unknown.
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The symptoms of MND vary depending on the type of MND. ALS is the most common of these diseases and affects both upper and lower motor neurons; it progresses quickly, and its early symptoms include muscle weakness, stiffness, spasticity and clonus. ALS is also associated with a progressively worsening respiratory function. Progressive bulbar palsy, progressive muscular atrophy and primary lateral sclerosis all progress slowly. These disorders affect LMNs, which extend from the brainstem to the lower part of the spinal cord and then to the muscles used for speech and swallowing.
Other inherited MNDs include spinal muscular atrophy, which affects UMNs and is characterised by the tightening of the muscles, and the congenital spinal muscular atrophy with arthrogryposis, which is very rare and appears at birth, and is caused by mutations in the gene SMA1. The symptoms of these diseases are similar but are more slowly progressive.
If you have a close relative who has MND, it’s important to see your GP as you may be at risk of developing the condition. Your GP can refer you for genetic counselling to discuss your risks and the tests that are available. Your GP can help you to access support services, and may also be able to recommend specialists and clinics. You can also talk to your GP if you are concerned about developing frontotemporal dementia, as these conditions often develop together.
Diagnosis
MND happens when specialist nerve cells in the brain and spinal cord stop working properly and start to die, causing weakness that gets gradually worse. There is no cure but there are ways to help manage the symptoms. People live with MND for years and may need help to walk, talk, swallow or breathe. It is known by several names, including motor neurone disease (MND) and Amyotrophic Lateral Sclerosis (ALS). ALS is the most common form of MND in the UK, but many people also use it to refer to the broader group of diseases which include Progressive Bulbar Palsy (PBP), Primary Lateral Sclerosis (PLS) and Hereditary Spastic Paraplegia (HSP).
MND affects both upper and lower motor neurons. It causes them to weaken and waste, which makes it difficult to walk, speak, chew and breathe. The symptoms develop gradually over weeks or months, and they tend to appear on one side of the body first. In some cases, the condition can be fatal.
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Research is taking place to find a way of slowing or stopping the disease, but it’s not yet possible to cure it. It’s important to see your GP if you have early signs of MND, such as muscle weakness. This can help to ensure that you get the right care and support.
Motor neurone diseases can affect adults and children. They are usually caused by specific gene mutations, but in a few cases they can run in families, as with the most common type of MND, ALS. It is also possible for symptoms to appear at any age, especially in young adults – this is called juvenile MND or jALS.
It is thought that there are over 25 genes and loci involved in MND. Research has identified that four of these – named C9ORF72, TARDBP, SOD1 and FUS – are associated with a higher risk of developing the disease. It is not yet known why these genes or locations are affected, but it is likely that they may play a role in the progression of the disease. It is also possible that environmental factors can trigger the disease.
Treatment
Currently there is no cure for motor neurone disease, but treatments can help ease symptoms and improve quality of life. They can include physical and occupational therapy, breathing machines for sleep and speech synthesisers. Some patients also benefit from dietary advice and nutritional supplements. Research into the condition is aimed at developing new treatments and enhancing care.
Motor neurons are nerve cells that send signals to muscles to make them move. When they stop working, the muscles get weaker (muscle atrophy or wasting) and are less active, which makes walking and moving more difficult. Other problems such as swallowing and breathing can develop. People with MND may also have a tremor or muscle spasticity, which is when the muscles get stiff and uncontrolled. They may also develop abnormal twitches called fasciculations.
Different types of MND occur and progress slightly differently. The four main types are amyotrophic lateral sclerosis (ALS), progressive muscular atrophy, primary lateral sclerosis and spinal muscular atrophy. Inherited forms of the disease develop in children and are caused by changes in a gene. These are known as hereditary motor neurone diseases and include spinal muscular atrophy type I, II and III and a form of the disease called Leigh Syndrome.
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The GP should be notified if a person is experiencing early symptoms of the disease, as they can refer to a specialist. It is important that MND is diagnosed as early as possible because of the potential impact it can have on a person’s quality of life. The GP can discuss this with the patient and offer genetic counselling to see whether family history is relevant to the condition.
MND is a result of degeneration of motor neurons in the brain and spinal cord. It can be sporadic or run in families and is associated with ageing, but the symptoms usually appear in middle and old age. Inherited forms of the disease can cause a younger presentation and are characterised by a mixture of upper and lower motor neuron features. The most common hereditary MND is spinal muscular atrophy (SMA). Research has shown that the amount of a protein called SMN2 affects the age at which SMA appears, the severity and progression of the disease throughout a person’s lifetime, and its response to treatment.
Prevention
Motor neuron diseases are a group of progressive neuromuscular disorders that cause progressively worsening weakness and muscle wasting. They are the most common cause of death in adults. Symptoms can range from mild to severe and can affect both upper and lower motor neurons. The most well known is amyotrophic lateral sclerosis (ALS), but other diseases in this group include spinal muscular atrophy (SMA), inherited bulbar muscular atrophy, Kennedy disease and poliomyelitis.
MNDs are caused by a breakdown of specialist nerve cells in the brain and spinal cord called motor neurones. The motor neurones control movement, speech and breathing. MNDs progress gradually over weeks and months, affecting one side of the body at a time, then the other. As the MND gets worse, you may need to use a wheelchair or ventilator to help with breathing and swallowing.
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Diagnosis of MND is based on history, examination and electrodiagnostic tests. Physiotherapy can also be helpful. In the early stages, treatment is supportive and focuses on helping with everyday activities, exercise, dysphagia, spasticity, sialorrhea, nutrition, breathing management and communication augmentation.
The onset of MND is usually insidious and the precise pattern depends upon the area of the CNS affected. In ALS, degeneration of the upper and lower motor neurones leads to weakness and muscle wasting. In familial ALS, mutations in the SMN1 gene on chromosome 5q12.2-q13.3 lead to a reduction in the production of full-length SMN protein. Other genetic MNDs include infantile spinal muscular atrophy, Kennedy disease and inherited bulbar muscular atrophy (inherited LMNA, inherited SMA, late-onset Tay Sachs, or LOTS), all of which have characteristic features on physical examination.
There are many other forms of MND that have been described, but their clinical characteristics differ widely. In general, they are characterized by the involvement of anterior horn cells in the spinal cord and motor nuclei in the brainstem. Some have localized distribution (Moebius syndrome and congenital cervical spinal muscular atrophy) while others are more generalized (ALS, SMA, CIDP and PPMD). The cause of most MNDs remains unknown. Research is ongoing to understand the underlying mechanisms of MNDs and develop new treatments.
