Planning for the What Ifs – Multiple System Atrophy

APDA Living with Parkinson's Planning for the What Ifs – Multiple System Atrophy

Advanced Parkinson’s and Multiple System Atrophy

As part of our Planning for the What Ifs series, today we continue to expand the definition of advanced Parkinson’s disease (PD) by discussing one of the atypical parkinsonian syndromes. In a past blog we explored two other atypical parkinsonian syndromes – Progressive supranuclear palsy and Corticobasal degeneration. Today we will discuss Multiple System Atrophy (MSA).

Clinical features and symptoms of MSA

MSA is a complex disease that, as its name suggests, is characterized by the degeneration of multiple neurologic systems. Severity and range of symptoms can vary dramatically. However, in general, progression of MSA is much more rapid than in PD and about 50% of people with MSA are wheelchair bound 5-6 years after diagnosis. In addition, MSA is much less common than PD. For every person with MSA in the population, there are 40 people with PD. Unlike PD which affects men more commonly than women, MSA affects men and women equally.

All people with MSA have autonomic failure, or dysfunction in neurologic systems that control the automatic processes of the body such as blood pressure, urination, sweating and bowel function.

In addition, people with MSA typically have parkinsonism, a set of symptoms including slowness, stiffness, tremor, and problems with walking and balance which are also present in PD. When these symptoms manifest as part of PD, they are responsive to levodopa treatment, whereas when they manifest as part of MSA, they are typically minimally responsive or not responsive to levodopa treatment. People with MSA can also have dysfunction in the cerebellar system, the brain system that controls accuracy of movement. Because of the variability of symptoms, MSA is often divided into two major categories: MSA-P (parkinsonian type) and MSA-C (cerebellar type). Of note, there can also be dysfunction of the pyramidal system, a third brain system that controls voluntary movement. Often people with MSA have neurologic impairment from a combination of degeneration of all these systems.

Autonomic dysfunction

Autonomic dysfunction is arguably the most characteristic problem of MSA. It must be emphasized however, that autonomic dysfunction is commonplace in PD as well, so by itself, may not be able to distinguish between the two diseases.

Common manifestations of autonomic dysfunction in MSA include:

  • Orthostatic hypotension
    • Inability to regulate blood pressure properly, leading to falls in blood pressure upon changing head position (moving from lying to sitting or sitting to standing). This can lead to lightheadedness and even passing out.
  • Urinary dysfunction
    • Urinary frequency
    • Urinary urgency
    • Urinary incontinence
  • Bowel dysfunction
    • Constipation
    • Fecal incontinence
  • Sweating abnormalities
    • Reduced sweating leading to heat intolerance and impaired temperature control
  • Erectile dysfunction

Pathology

Similar to PD, MSA is characterized pathologically by abnormal accumulations of alpha-synuclein. However, whereas in PD the alpha-synuclein accumulates in the nerve cells, in MSA it accumulates in the glial cells. Glial cells are the helper cells of the brain which allow the nerves to function properly.

Distinguishing between Parkinson’s disease and MSA

It can be challenging to differentiate between PD and MSA. Early on in the course of the illness, MSA can manifest with mild parkinsonism and autonomic dysfunction. These clinical features are also often present in PD. Furthermore, in the beginning, the parkinsonism of MSA can be minimally responsive to levodopa, complicating the distinction between the diseases even more. Both diseases have a high rate of REM behavior sleep disorder (RBD). Therefore, it is very common for someone with MSA to initially receive a diagnosis of PD. (It is important to note however, that rest tremor which is present in about 75% of people with PD, is not common in MSA and is present in less than 10% of cases.)

Over time, clinical features may develop that are not as common in PD and may suggest MSA as a diagnosis. However, although these features are not as common in PD, they can still be present in PD, so diagnosis remains difficult. The more features that are uncommon in PD that are present, the more the clinical situation warrants the consideration of MSA as the diagnosis. These “red flags” include:

  • Poor levodopa response
  • Rapid decline
  • Facial dystonia (or abnormal posturing of facial muscles) from levodopa
  • Sleep-disordered breathing such as obstructive sleep apnea
  • Inspiratory stridor (a high-pitched sound during intake of breath) during daytime or sleep (laryngeal dystonia)
  • Jerky tremor when performing an action
  • Axial postural abnormalities (e.g. severely bent neck, bend at the waist, tilt at the waist)
  • Cold, darkened/reddened hands and feet
  • Severe difficulty with speech
  • Severe difficulty with swallowing
  • Pseudobulbar affect – the Involuntary and uncontrollable reactions of laughing or crying that are out of proportion to the cause of the emotional response

Diagnosing MSA

It is clear from the above discussion, that an important area of investigation is the development of ways to distinguish between PD and MSA. Currently, there are some tests that can help distinguish between the two. An MRI of the brain, which is typically not used to diagnose PD, may have certain features that make a diagnosis of MSA more likely. Positron emission tomography (PET), using Fluorodeoxyglucose (FDG), measures glucose utilization in the brain and is being investigated as a way to distinguish between MSA and PD. It is important to note that DaTSCAN imaging does NOT distinguish between MSA and PD. In both diseases, the DaTSCAN will be abnormal.

Imaging part of the heart’s nervous system, using the radioactive tracer, [123I]meta-iodo-benzyl-guanidine, (MIBG), holds promise in distinguishing between MSA and PD. In PD, MIBG detection in the heart is diminished or absent, whereas in MSA, the MIBG detection is typically normal. MIBG cardiac imaging is still considered an experimental procedure for this purpose.

In addition to testing that can help distinguish between PD and MSA, there is testing available to ascertain the extent of autonomic dysfunction. A tilt table test for example can ascertain the extent of a person’s orthostatic hypotension. Other testing can measure other functions of the autonomic nervous system such as sweating and urination. A sleep study can help to diagnose the sleep abnormalities that are commonly associated with MSA such as RBD, and sleep apnea.

Treatment for MSA

There are no specific treatments for MSA and treatments are therefore focused on controlling symptoms and maximizing quality of life. Many courses of treatment are similar to PD.

  • Parkinsonism: Physical therapy (PT) can be vital to maximize function. In addition, one third of patients respond at least partially or initially to levodopa and it should therefore be considered for anyone diagnosed with MSA. Treatment however, can be difficult because levodopa can exacerbate orthostatic hypotension. Other anti-parkinsonian medications such as dopamine agonists or amantadine can be tried as well, but they too, can worsen orthostatic hypotension.
  • Cerebellar dysfunction cannot be treated pharmacologically and PT is the cornerstone of treatment for this aspect of MSA.
  • Orthostatic hypotension can be treated in the same ways that it is treated when it is a symptom of PD. These measures include:
    • Implementing dietary changes to increase fluid and salt intake. This may include ingestion of salt tabs.
    • Avoiding foods that lower blood pressure such as caffeine, carbohydrate-rich meals and alcohol
    • Changing head position slowly to allow more time for blood pressure to adapt
    • Elevating the head of the bed at night
    • Wearing compression stockings or an abdominal binder
    • Using medication such as midodrine, fludrocortisone or droxidopa
  • Urinary dysfunction can also be treated in the same ways that it is treated when it is a symptom of PD. These measures include:
    • Strengthening the muscles that control the bladder through PT and pelvic floor exercises.
    • Using medications for overactive bladder. These medications have to be chosen carefully to minimize side effects that can affect cognition and blood pressure.
  • Bowel dysfunction can also be treated in the same ways that it is treated when it is a symptom of PD. These measures include:
    • Optimizing diet to help with constipation
    • Maximizing exercise and activity
    • Using various over-the-counter and prescription medications
  • Sleep-disordered breathing
    • Continuous positive airway pressure (CPAP) can be used for sleep apnea and laryngeal stridor
    • Sometimes tracheostomy (in which a tube is placed in the trachea to allow for unimpeded breathing) is performed for laryngeal stridor
  • Pseudobulbar affect can be treated with a combination of dextromethorphan hydrobromide and quinidine sulfate (brand name Nudexta)
  • Speech and swallow difficulties can be improved by implementing speech therapy and swallow therapy

Clinical trials for MSA

Participation in clinical trials may be an option for certain patients and can be a way for people with MSA to collaborate with the research community to advance potential new treatments. A number of clinical trials for MSA are currently underway and you can learn more about them to help decide if getting involved is right for you.

Tips and Takeaways

  • Multiple system atrophy (MSA) is an atypical parkinsonian syndrome that shares a number of similarities with PD
  • Diagnosing MSA can be difficult early in the disease course, and it is often misdiagnosed as PD
  • MSA is much less common than PD and typically results in a more rapid decline than PD
  • As MSA progresses, it can affect multiple neurologic systems resulting in autonomic dysfunction, parkinsonism and/or cerebellar dysfunction
  • Treatment of MSA focuses on symptom management
  • People with MSA should discuss their eligibility for any clinical trials with their movement disorders physician

More from our series: Planning for the What-ifs

Parkinson’s Disease: Planning for the What Ifs is a special series within this blog that presents information about advanced PD symptoms. PD affects people very differently and, for some, the disease will not progress to advanced stages, but it can be helpful to educate yourself about the possibilities; and those who are dealing with advanced PD right now may find this series particularly useful.

In previous blogs, we addressed the mental health issues of advanced PD which include:

We also addressed other symptoms of advancing disease including:

We encourage you to check out these past blog posts for more information about advanced PD.

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