All about Multiple System Atrophy (MSA)

Not many people have heard of multiple system atrophy (MSA). However, according to the MSA Trust, in the UK and Ireland, around 3,500 people live with the condition. This means that most people won’t have come across it unless they know someone with the condition – and this can include some healthcare professionals. This is one of the reasons why the MSA Trust is active in its field with aims to not only raise awareness but also to increase understanding of MSA and what it means for those affected.

What is multiple system atrophy?

Multiple system atrophy is commonly abbreviated to MSA and it affects adult men and women. It’s a rare and progressive neurological disorder that affects the autonomic nervous system. It is caused by the degeneration or atrophy of the nerve cells. Atrophy simply means ‘shrinking’. This can be in several areas within the brain.

Because of the atrophy in the nerve cells in the brain, MSA is characterised by symptoms that affect movement, balance and coordination. There are also dysfunctions in the autonomic nervous system that controls a person’s automatic functions like blood pressure, heart rate, bladder function and digestion.

To break it down further, we can analyse the meaning behind the name:

• Multiple – meaning many.
• System – meaning structures in the body that control certain functions.
• Atrophy – cell loss and shrinkage.

To put it together, the condition is where many systems in the body that control our functions are losing cells or have cells that are damaged and shrinking. The most commonly affected areas are the cerebellum, brain stem and basal ganglia parts of the brain.

Because MSA is a degenerative disorder, it can progress rapidly and lead to a significant disability in affected individuals.

There are two main subtypes that are based on the predominant symptoms:

• MSA-P: Multiple system atrophy with Parkinsonian features.
• MSA-C: Multiple system atrophy with cerebellar features.

Multiple system atrophy was previously called ‘Shy-Drager Syndrome’ with the term MSA first introduced in 1969. It wasn’t until 1969 that the multiple system atrophy was widely used as its name after an international consensus of many experts. This was also when the identification of the subtypes MSA-P and MSA-C arose.

Types of MSA

As mentioned, there are two main types of multiple system atrophy: MSA-P and MSA-C. The types of symptoms a sufferer experiences are what define the subtype of their disease.

MSA with Parkinsonian features (MSA-P)

This type of MSA involves symptoms that are similar to those of Parkinson’s disease – hence its name.

These symptoms include:

• Tremors.
• Rigidity.
• Slow movements.
• Difficulty with balance.
• Falls.
• Postural instability.

MSA with Cerebellar features (MSA-C)

MSA with cerebellar features is characterised by symptoms that affect coordination and balance, including:

• Difficulty walking.
• Poor coordination.
• Slurred speech.
• Less prominent tremors.
• Less prominent muscle rigidity.

Despite the different subtypes, some individuals with MSA may have a rare combination of both Parkinsonian features and cerebellar features. Their condition is sometimes classified as MSA with fixed features. Additionally, there is a rare form of MSA named MSA-D. This is called MSA associated with pure autonomic failure, affecting primarily the autonomic nervous systems.

Symptoms of this type include:

• Orthostatic hypotension.
• Bladder dysfunction.
• Constipation.

Causes of MSA

The exact cause of multiple system atrophy is not known. It is believed to be a combination of genetic and environmental factors. It’s a rare disorder and is thought to be due to the effects of an abnormal accumulation of a protein called alpha-synuclein in certain areas of the brain which leads to the degeneration of nerve cells. These ‘atrophied’ or ‘shrunk’ nerve cells can sometimes be visualised on MRI scans. The loss of nerve cells causes the brain to ‘shrink’ in affected areas.

Everyone has alpha-synuclein in their brain. But it’s the abnormal deposits of it in the brain’s control-centre cells that cause the difficulties and symptoms experienced with MSA. It’s still not quite clear what causes alpha-synuclein to accumulate in the cells of people with MSA. Likewise, how the damage progresses is also unclear and is unique for each person affected.

An old theory is that there has previously been some trauma in the brain’s grey matter. However, this theory is now largely not thought to be the case. There has been some research that has shown links with environmental factors such as toxins being higher in those affected by MSA compared with those unaffected.

One small study showed that those affected by MSA had higher rates of toxin exposure such as to metal dust, pesticides, organic solvents and plastics compared with a control group. Having said that, when the relatives were surveyed, the relatives of the MSA patients had more MSA symptoms than the relatives of the control group, which also suggests that there is some genetic vulnerability to developing MSA with it perhaps being activated by exposure to environmental toxins.

Another study showed that families with more than one person affected by MSA had an autosomal recessive inheritance of the disease, with a single nucleotide polymorphism within the genetic coding for alpha-synuclein. In other words, the affected individuals had inherited a ‘faulty’ genetic code from their parents, meaning their brains began to accumulate too much alpha-synuclein in their brain cells.

However, despite this risk, most cases of MSA are not thought to be directly inherited and occur sporadically. It’s clear that the causes of MSA are not yet well understood. Ongoing research is focused on identifying the underlying mechanisms that lead to its development and progression.

Who is at risk of MSA?

MSA is a rare disorder with its exact risk factors generally unknown. However, certain factors mean that someone is more likely to develop the disease, but these are not definitive.

These include:

• Genetics – MSA typically occurs randomly and is not directly inherited, some studies have identified certain genes that are associated with an increased tendency to develop the condition.
• Age – MSA typically occurs in people over 50 years of age. The majority of people are diagnosed somewhere between the ages of 50 and 60.
• Sex – whilst both sexes are affected, MSA is slightly more common in men than women.
• Exposure to toxins – some research has highlighted an increased propensity of MSA in those who have been exposed to certain toxins such as industrial chemicals, pesticides, plastics and metal dust.
• Viral infections – other research has suggested that there may also be a possible link between certain viral infections and the development of MSA. However, much more research is needed to fully understand this relationship.

Overall, the risk factors for multiple system atrophy are not well understood and much more research is needed to identify the underlying causes and the risk factors associated with its development.

What are the symptoms of MSA?

The symptoms of MSA will depend on the subtype of the condition. However, for men, the first symptom noticed is often erectile dysfunction (an inability to achieve and/or maintain an erection). However, given that this is a fairly common occurrence in men of a certain age or indeed is associated with other conditions, it may not be obvious to a doctor that it has a neurological cause at this stage.

Other early symptoms in both men and women include bladder problems such as urinary frequency, urgency, needing to urinate during the night (nocturia) and urinary retention – where a person can’t empty their bladder completely. However, as with erectile dysfunction, these symptoms are also often linked to other causes like ageing.

When people look back to the time of the onset of their symptoms, they may also reflect on how they perhaps felt slow and stiff or that their handwriting worsened. For some people, being more unsteady on their feet or becoming clumsier was an early indication of the condition. Likewise, if the condition has affected a person’s blood pressure, they may experience feeling dizzy when they stand up or may have had fainting episodes.

Progression

The early symptoms described above are often ascribed to other conditions or just to a general deterioration in older age, as is often expected. However, given MSA is a degenerative condition, the symptoms of the disease become more profound and pronounced gradually, and it is at this stage that their healthcare practitioner may begin to look to other causes.

At this more progressive stage, people begin to need more help with their activities of daily living. For some people, the progression of this stage is rapid; for others, it’s more gradual and less noticeable. Because everyone’s experience with MSA is different, it’s hard to predict how the disease will progress.

Common symptoms

There are many common symptoms shared between individuals who have MSA. However, the symptomology greatly depends on the subtype of MSA.

• MSA-P (Parkinsonism) symptoms may include:
  – Feeling stiff and slow when moving.
  – Difficulty in beginning movements.
  – Handwriting difficulties where writing becomes spidery and small.
  – Difficulties turning over when in bed.
• MSA-C (Cerebellar) symptoms may include:
  – Increased clumsiness and dropping things.
  – Difficulty with buttons, fastenings and zips.
  – Unbalance without support.
  – Unsteadiness when out or in crowded areas.
  – Slurred speech.
  – Handwriting difficulties.
• Autonomic symptoms may include:
  – Sexual dysfunction (erectile dysfunction).
  – Bladder problems.
  – Problems with blood pressure such as dizziness or fainting.
  – Neck and shoulder pain (‘coat-hanger’ pain).
  – Changes in bowel function.
  – Cold feet and hands.
  – Problems with sweating.
• Other symptoms that some people may experience include:
  – Emotional lability such as uncontrollable crying or laughing.
  – Nightmares.
  – Restless sleep.
  – Arm and leg weakness.
  – Excessive snoring.
  – Noisy breathing.
  – Sighing unintentionally.
  – Blurred vision.
  – Quiet, weak voice.
  – Difficulty with swallowing, chewing and coughing when eating.

Given that the condition is very individual, sufferers of MSA may only experience a few of these symptoms or may have many, depending on the stage and progression of the disease. For many, the symptoms cause a significant disability and reduced quality of life, which can ultimately lead to death.

How common is MSA?

According to some research, the incidence of MSA in the USA is estimated to be around 0.6 cases per 100,000 people each year. This equates to around 1,900 people diagnosed every year. A study in London also gave a figure (adjusted by age) of 4.4 people living with the condition per 100,000 at any one time.

The MSA Trust states that there are around 3,300 people currently living with the condition across the UK, making it an extremely rare condition that, as mentioned, even many healthcare professionals are not familiar with. It is much less common than other neurodegenerative disorders such as Parkinson’s disease, and it is often misdiagnosed or undiagnosed due to its rarity and overlapping symptoms with other diseases. Parkinson’s disease is around 45 times more common than MSA and affects about 210 people per 100,000.

As far as the different subtypes are concerned, around 60% of cases fall into the MSA-P subtype with the remaining 40% being MSA-C.

As more is learned about MSA, it is becoming easier to spot and diagnose affected individuals – though this process can and does still take time, often many years! Overall, while MSA is a rare disorder, it can be a devastating and progressive disease that significantly impacts a person’s quality of life.

Complications of MSA

MSA is a progressive and debilitating disorder that can result in many complications depending on the type and the systems in the body that are mostly affected.

Some of the common complications include:

• Falls and injuries due to balance and mobility problems.
• Autonomic dysfunctions affecting the bladder, bowels, sexual function and blood pressure.
• Speech and swallowing difficulties which can lead to aspiration of food or fluids into the lungs, increasing the risk of pneumonia.
• Respiratory problems such as aspiration pneumonia (see above) or respiratory failure.
• Cognitive decline. Some individuals are affected by memory loss or executive function difficulties such as with problem-solving or planning tasks.
• Emotional and social problems. MSA can lead to depression, anxiety and social isolation which can all have a significant impact on an individual’s quality of life.

Overall, the complications of MSA can lead to a deterioration in the individual’s quality of life and ultimately premature death. Managing the symptoms and complications often requires a multi-disciplinary approach with input from neurologists, physiotherapists, speech therapists and occupational therapists.

How is multiple system atrophy diagnosed?

Diagnosis of multiple system atrophy is often fraught with difficulty. Some General Practitioners may not be familiar with the condition as it is so rare. Its diagnosis often depends on a specialist (such as a neurologist) recognising a specific combination of symptoms using certain criteria. Unfortunately, many neurological conditions often appear similar in their earlier stages, so it’s often a case of ruling out other conditions first before diagnosing MSA.

Quite often a diagnosis is made after an MRI scan, but in some cases, MRI scans can appear normal. Often, a neurologist will take a clinical evaluation to assess the associated symptoms as a first step to diagnosis. This evaluation will include taking a detailed medical history, including the onset and progression of symptoms, and a physical examination to assess the motor, autonomic and cognitive symptoms that are associated with MSA and other neurological conditions.

Autonomic testing evaluates the function of the autonomic nervous system and includes blood pressure monitoring during postural changes or a tilt table test for orthostatic hypotension.

As mentioned, imaging studies such as MRI scans may be carried out or in some cases PET scans (positron emission tomography) to assess for changes in the brain structure and function. Additionally, blood tests are often carried out to rule out any other potential causes for the presenting symptoms such as thyroid dysfunction or vitamin deficiencies. In some rare cases, skin biopsies may be performed to look out for an accumulation of alpha-synuclein protein – the hallmark of MSA.

A diagnosis of MSA is typically made based on a combination of these factors including the presence of specific motor and autonomic symptoms, changes in imaging studies and excluding other potential causes for the symptoms. For this reason, it may take some time and many evaluations before a definitive diagnosis is reached. Diagnosing MSA early and accurately is important to ensure that the symptoms are managed effectively so individuals and their families can plan for the future.

Can MSA be treated?

Currently, there is no cure for multiple system atrophy. Treatment is primarily aimed at managing the symptoms of the disorder to improve quality of life. Treatment for MSA is therefore typically multifaceted and may involve medication, physical therapy and supportive care.

Professionals involved may include:

• Neurologists.
• Neurology nurse specialists.
• Physiotherapists.
• Speech and language therapists.
• Occupational therapists.
• Carer support.
• Palliative care specialists.
• Bladder and bowel specialists.
• Community nurses.
• Social workers and care services.
• Falls services and clinics.
• Dieticians.
• Neuropsychologists.
• Counsellors.

Most people are generally supported by their GP who often acts as a coordinator for a person’s care and will refer them to different specialists. Sometimes the specialists at the hospital will coordinate care for different aspects of the treatment and support that someone needs.

Medications

Medications are often used to manage the motor and autonomic symptoms of MSA. For motor symptoms, medications that are used to treat Parkinson’s disease such as Levodopa, Amantadine, dopamine agonists and MAO-B inhibitors may be prescribed. For autonomic symptoms, Fludrocortisone or Midodrine may well be used to manage blood pressure and improve urinary function.

Physical therapy

Physical therapy such as physiotherapy can help to improve mobility, balance and coordination and can therefore help to prevent falls and injuries. A speech therapist may also offer physical therapy if there are speech and swallowing difficulties.

Occupational therapy

Occupational therapy services will be able to provide support with aids and equipment that may make an individual’s life easier. This may include walking frames, walking sticks, bath supports, and grab rails, for example.

Supportive care

Supportive care is an important aspect of managing MSA and may involve things such as a high-salt diet, hydration and compression stockings to manage orthostatic hypotension. In more advanced states, hospice care may be necessary to provide comfort and support for both the individual and their family.

Complementary therapies

Some people find complementary therapies can help them cope with their condition and help them manage the symptoms. These treatments may include massage, yoga, reiki, Pilates, tai chi, aromatherapy, reflexology, homoeopathy and acupuncture.

Experimental therapies

Whilst these are very much in their early stages of development, experimental therapies may well be offered. Ongoing trials are exploring new treatment options for MSA including the use of stem cells and gene therapy.

Whilst there is currently no cure for MSA, early diagnosis and management of the symptoms can help improve the quality of life in those affected and may help to slow the progression of the disease. A team-based approach involving many health professionals can help to provide comprehensive and individualised care for those affected.

Help and support

There are various resources available to those suffering from multiple system atrophy and their families.

These include:

• MSA support groups
  – The MSA Trust has online support groups that take place on Zoom and are attended by an MSA Trust healthcare specialist. There are also digital coffee mornings and in-person support groups.
• Healthcare professionals
  – If you or your family need support with MSA, your GP or treating neurologist will be able to offer advice and support for your individual needs and circumstances as well as recommend other avenues of accessing support that are local to you.
• Caregiver support
  – Carers can often access support networks to help them cope with the additional responsibility of caring for someone with a degenerative condition. One sole person mustn’t be the only one responsible for caring for someone with MSA, although at times this is all that is possible. The MSA Trust has Health Care Specialists that help not just with the needs of the sufferer but also with their carers.
• Financial assistance
  – People with MSA and their families may face financial burdens related to their symptoms and inability to continue working if they are of working age. They may be entitled to certain benefits, attendance allowance and Personal Independence Payments (PIP).

Overall, seeking support is a crucial part of dealing with a diagnosis of MSA whether it affects you or whether you are supporting someone who is affected. With the right kind of support, families can navigate the challenges associated with multiple system atrophy and improve their quality of life.