Motor Neurone Disease MND

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What is MND

Motor Neurone Disease (MND) is the name given to the group of diseases in which the motor neurones undergo degeneration and die. Motor neuron diseases cause the nerves in the spine and brain to lose function over time. They are a rare but severe form of neurodegenerative disease. Some MNDs are inherited, however most causes of most MNDs are not known.  In sporadic or noninherited MNDs, environmental, toxic, viral, or genetic factors may be implicated.

MNDs are classified according to whether they are inherited or sporadic, and to whether degeneration affects upper motor neurons, lower motor neurons, or both. Common subtypes include

  • In adults, the most common MND is Amyotrophic lateral sclerosis (ALS), which affects both upper and lower motor neurons.  It has inherited and sporadic forms and can affect the arms, legs, or facial muscles. 
  • Primary lateral sclerosis (PLS) is a disease of the upper motor neurons
  • Progressive muscular atrophy (PMA) affects only lower motor neurons in the spinal cord
  • Progressive Bulbar Palsy (PBP), the lowest motor neurons of the brain stem are most affected, causing slurred speech and difficulty chewing and swallowing.  There are almost always mildly abnormal signs in the arms and legs.
  • Kennedy’s disease, also known as progressive spinobulbar muscular atrophy
  • Post-polio syndrome (PPS)
  • Spinal muscular atrophy (SMA) [1]

Although MND is the widely used generic term in the United Kingdom, Australia and parts of Europe, ALS is used more generically in the United States, Canada and South America.[2]

MND is also known as Lou Gehrig's disease in the US after a famous baseball player who died of the disease. The renowned English physicist Stephen Hawking lived with ALS for many decades until his death in March 2018.[3] 

The below video is a brief overview of the condition and the NICE guidelines on MND

[4]


Risk Factors

MNDs

  • Mccurs in adults or children, depending on the type.
  • more likely to affect men than women.
  • Inherited forms of the condition may be present at birth
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  • Most likely to appear after the age of 40 years, usually between 55–75 years.
  • The various types may have different risk factors. SMA is always hereditary, but this is not true for all forms of MND.
  • According to NINDS, around 10% of ALS cases in the United States are hereditary.
  • Veterans appear to have a 1.5–2 times higher chance of developing ALS than non-veterans. This may indicate that exposure to certain toxins increases the risk of having ALS.[3] (image - agent orange being stored)
  • A 2012 studyTrusted Source found that footballers have a higher risk of dying from ALS, Alzheimer's disease, and other neurodegenerative diseases, compared with other people. Experts think that this could indicate a link with recurrent head trauma[3]

Clinical Presentation

Early symptoms may be mild and include:

  • Stumbling due to weakness of the leg muscles
  • Difficulty holding objects caused by weakness of the hand muscles
  • Slurring of speech or swallowing difficulties due to weakness of the tongue and throat muscles
  • Cramps and muscle twitching

As the disease progresses symptoms may include:

  • Breathing difficulties from decreased lung capacity caused by muscle weakness
  • Fatigue caused by muscle exhaustion, decreased lung capacity, metabolic changes, weight loss and reduced food intake
  • Insomnia caused by discomfort, pain from stiff joints and muscles, excessive saliva, dry mouth or breathing problems
  • Mild changes in cognitive skills and processes and/or behavioural change
  • Fronto-temporal cognitive changes (a type of dementia), which is prominent in 5-10% of MND cases
  • Excessive laughing or crying due to damage to the upper motor neurones
  • Some pain or discomfort

Diagnostic Procedures

Motor neurone disease (MND) is difficult to diagnose as the initial symptoms can be similar to many other conditions[3].

Neurologists use a series of tests to eliminate other conditions before making a definitive diagnosis of MND.

Tests may include:

  • Blood tests to look for a rise in a creatine kinase, which is produced when muscle breaks down.
  • Nerve conduction studies (NCS), which involve taping electrodes over nerves and recording muscle activity when nerves are stimulated by electrical impulses.
  • Electromyography (EMG) to measure their electrical activity of muscles
  • Magnetic Resonance Imagery (MRI) scans, takes images of the internal structures of the body and can show up damaged areas. An MRI scan will not diagnose Motor Neurone Disease, as the damage caused by this disease does not show up on this scan. However, it may be used to eliminate other conditions which can mimic symptoms of MND.[2]

Management

There is no cure or standard treatment for the MNDs.  Symptomatic and supportive treatment can help people be more comfortable while maintaining their quality of life.  Multidisciplinary clinics, with specialists from neurology, physical therapy, respiratory therapy, and social work are particularly important in the care of individuals with MNDs[1].

Dietician - Proper nutrition and a balanced diet are essential to maintaining weight and strength.  People who cannot chew or swallow may require insertion of a feeding tube.  In ALS, insertion of a percutaneous gastronomy tube (to help with feeding) is frequently carried out even before it is needed, when the individual is strong enough to undergo this minor surgery.

Medication

The drug riluzole (Rilutek®) has been approved by the U.S. Food and Drug Administration (FDA) to treat ALS, prolongs life by 2-3 months but does not relieve symptoms.  The drug reduces the body's natural production of the neurotransmitter glutamate, which carries signals to the motor neurons.  Scientists believe that too much glutamate can harm motor neurons and inhibit nerve signaling.  The FDA has also approved the use of edaravone (Radicava™) to slow the clinicla decline seen in individuals with ALS.

The FDA has approved nusinersen (Spinraza ™) as the first drug approved to treat children and adults with spinal muscular atrophy. The drug is administered by intrathecal injection into the fluid surrounding the spinal cord. It is designed to increase production of the full-length SMN protein, which is critical for the maintenance of motor neurons.

Other medicines may help with symptoms.  Muscle relaxants such as baclofen, tizanidine, and the benzodiazepines may reduce spasticity.  Botulinum toxin may be used to treat jaw spasms or drooling.  Excessive saliva can be treated with amitriptyline, glycopyolate, and atropine or by botulinum injections into the salivary glands.  Combinations of dextromethorphan and quinidine have been shown to reduce pseudobulbar affect.  Anticonvulsants and nonsteroidal anti-inflammatory drugs may help relieve pain, and antidepressants may be helpful in treating depression.  Panic attacks can be treated with benzodiazepines.  Some individuals may eventually require stronger medicines such as morphine to cope with musculoskeletal abnormalities or pain, and opiates are used to provide comfort care in terminal stages of the disease.

Physiotherapy

Physical therapy rehabilitation may help to improve posture, prevent joint immobility, and slow muscle weakness and atrophy. 

  • Stretching and strengthening exercises may help reduce spasticity, increase range of motion, and keep circulation flowing. 
  • Applying heat may relieve muscle pain. 
  • Assistive devices such as supports or braces, orthotics, speech synthesizers, and wheelchairs may help some people retain independence.
  • Non-invasive ventilation at night can prevent apnea in sleep, and some individuals may also require assisted ventilation due to muscle weakness in the neck, throat, and chest during daytime.

Palliative Care

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Palliative care often becomes very important in the care of patients with motor neurone disease. There is increasing emphasis on the multidisciplinary assessment and support of patients within guidelines, supported by research. This includes the telling of the diagnosis, the assessment and management of symptoms, consideration of interventions, such as gastrostomy and ventilatory support, and care at the end of life. The aim of palliative care is to enable patients, and their families, to maintain as good a quality of life as possible and helping to ensure a peaceful death.

There will need to be a collaborative approach involving many services – including primary/family/home care but many specialist services, such as gastroenterology, respiratory medicine, neuropsychology as well as neurology and palliative care services. It is important to ensure that these services provide co-ordinated care and many suggest a specific/key person or team with whom the patient and family can have regular contact.[5]

Prognosis

Prognosis varies depending on the type of MND and the age of onset.  Some MNDs, such as PLS or Kennedy’s disease, are not fatal and progress slowly.  People with SMA may appear to be stable for long periods, but improvement should not be expected.  Some MNDs, such as ALS and some forms of SMA, are fatal.

The Future

The last decade has seen major improvements in patient care, but also rapid scientific advances, so that rational therapies based on key pathogenic mechanisms now seem plausible.[6]

Research is focused on creating new and better medicines, developing potential treatments with stem cells, and identifying genetic mutations and other factors that may influence the development of these diseases.[1]

  • Stem cells

Scientists are developing a broad range of model systems in animals and cells to investigate disease processes and expedite the testing of potential therapies.  Since stem cells have the ability to develop into many different cell types, including motor neuron and support cells, they could potentially repair the nerve damage caused by MNDs.

  • Gene therapy

Scientists have used gene therapy to halt motor neuron destruction and slow disease progression in mouse models of SMA and inherited ALS.  A small clinical trial of SMN gene replacement therapy is now underway in individuals with SMA.

Scientists are using advanced sequencing technologies to identify new gene mutations that are associated with MNDs.  These gene discoveries are providing new insights into the cellular disease processes and possible intervention points for therapy.

  • Drug interventions

Researchers are testing whether different drugs, agents, or interventions are safe and effective in slowing the progression of MNDs.

References

  1. 1.0 1.1 1.2 NIH MND fact sheet Available from: https://www.ninds.nih.gov/disorders/patient-caregiver-education/fact-sheets/motor-neuron-diseases-fact-sheet#3144_7 (last accessed 15.12.2019)
  2. 2.0 2.1 MND Australia What is MND Available from: https://www.mndaust.asn.au/Get-informed/What-is-MND (last accessed 15.12.2019)
  3. 3.0 3.1 3.2 3.3 Medical news today What is MND Available from: https://www.medicalnewstoday.com/articles/164342.php (last accessed 15.12.2019)
  4. NICE NICE guideline on Motor Neurone Disease - why it's so important Available from: https://www.youtube.com/watch?v=KEZUwIjJlDc&feature=youtu.be (last accessed 15.12.2019)
  5. Oliver DJ. Palliative care in motor neurone disease: where are we now?. Palliative Care: Research and Treatment. 2019 Jan;12:1178224218813914. Available from: https://journals.sagepub.com/doi/full/10.1177/1178224218813914 (last accessed 15.12.2019)
  6. Bäumer D, Talbot K, Turner MR. Advances in motor neurone disease. Journal of the Royal Society of Medicine. 2014 Jan;107(1):14-21. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3883149/ (last accessed 15.12.2019)