Introduction and Definitions
• Motor neurone disease (MND) is a condition that causes progressive weakness of the nervous system and eventually death, usually as a result of respiratory failure or aspiration
• The term MND covers a group of related diseases that affects both nerves and muscles because there is damage to the nerve cells that control muscle activity
• Motor neurone disease is a rare condition that affects around 2 in every 100,000 people each year in the UK.
• There are about 5,000 people living with the condition in the UK at any one time.
• There is no identifiable group at risk of MND, although more often it is diagnosed in people of European descent
• It is most frequently found in the second half of life, usually between the ages of 50 and 80
• 50% of people are often diagnosed when over the age of 70
• Below the age of 70 men are seen to be more affected than women
Types of MND
• There are four main types of MND, each affecting people in different ways
• Amyotrophic lateral sclerosis: This is the most common form, with both upper and lower motor neurone involvement. This form of the disease is characterised by weakness and wasting in the limbs. Someone may notice they are tripping when walking or dropping things. ALS can be divided into a familial form (i.e. the condition is inherited) and a sporadic form (i.e. the condition is not inherited). Sporadic ALS is the most common, accounting for about 90% of all people with the condition.
• Progressive muscular atrophy: Affects only a small proportion of people, mainly causing damage to the lower motor neurones. Early symptoms may be noticed as weakness or clumsiness of the hand.
• Bulbar palsy: Affects about a quarter of people diagnosed, and involves both the upper and lower motor neurones. Symptoms may include slurring of speech or difficulty swallowing
• Primary lateral sclerosis: A rare form of MND involving the upper motor neurones only, causing mainly weakness in the lower limbs
• There is no known cause that could explain all cases of MND or the distribution of MND worldwide
• One popular theory is that there are differences in susceptibility to MND, such as genetic predispositions and there are external factors such as toxins that can accelerate the disease process
• 5-10% of people, who have the inherited form of MND, their genetic makeup is more significant. Currently 13 genes carrying mistakes have been identified that can cause inherited MND.
• Most forms of MND are likely to be caused by many small contributory risk factors. Studies show that exposure to environmental factors might contribute to the development of MND. These studies have identified possible links with prior exposure to: mechanical and/or electrical trauma, military service, high levels of exercise, agricultural chemicals and variety of heavy metals.
• Possible causes could include glutamate, cell disruption, aggregates and lack of nutrients.
• Glutamate metabolism is affected in MND and it is believed that an increase in concentration of glutamate around the motor neurone is toxic, causing them to deteriorate.
• Cell disruption is also a possible cause. Research suggests that the transport systems in motor neurones become disrupted in motor neurone disease. This may contribute to the loss of normal nerve function.
• Aggregates are abnormal clumps of protein that develop inside motor neurones. They have been found in most cases of motor neurone disease. The clumps may disrupt the normal working of the motor neurones.
• There's evidence that in motor neurone disease neurotrophic factors are not produced in the correct way. This may make the motor neurones more vulnerable to damage and affect their function.
• MND affects motor neurone cells, that are concerned with motion and movement and they are responsible for moving our muscle
• MND affects both upper and lower motor neurons
• Upper motor neurons originate from the primary motor cortex of the cerebrum and possess long axons forming corticospinal and corticobulbar tracts
• Lower motor neurons originate in the brainstem and spinal cord and directly innervate skeletal muscles
• As the nerves deteriorate, they become too weak to make muscle fibres contract and this causes muscular weakness because control of the affected limbs are lost, and this can lead to poor mobility
• There are five main investigations used in the diagnosis of MND
• Electromyogram (EMG): This measures and analyses the electrical stimuli to various parts of the body (typically the long muscles of the forearm and hands). EMG patterns show where the long and short muscle fibres occur and where nerves might have degenerated
• MRI: MRIs can create a detailed image of most non-moving tissues such as the CNS
• CT: X-ray images are taken of the brain and spinal column to form images that are easier to analyse than one single image
• Muscle biopsy: This involves a small part of the muscle being taken, using a hollow core. The specimen of muscle fibre can then be assessed under a microscope to see if fibres are degenerated
• Lumbar puncture (spinal tap): a small amount of cerebrospinal fluid is extracted using a needle between the lower lumbar vertebrae of the spinal column, and this is then analysed for raised protein content but normal cells
• Currently there is only one drug that has been approved for the treatment of MND itself. Riluzole is the only drug that has completed clinical trials.
• The drug binds with glutamic acid and blocks effects as well as reducing the concentration of glutamate around the motor neurone.
• It is prescribed initially by a neurologist and it is taken as a 50mg capsule twice a day. The drug has shown that survival was improved.
• Treatment often involves management of different symptoms to maintain strength and abilities; this includes options such as physiotherapy and surgery.
• Physiotherapy can be offered as a treatment option to help reduce the physical disabilities caused by the progression of MND and surgery can include tracheostomies and gastrostomies, however all surgery in MND is aimed at alleviating disabilities only, rather than curing the disease itself.
• With very little in terms of treatment, survival after diagnosis is usually 2-5 years
• Although there are rare MND cases who survive for a decade or longer
• And the best known example is Professor Steven Hawking who has had MND for about 40 years