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What is Shy Drager Syndrome/MSA?
Shy-Drager Syndrome was first discovered in 1960 by Dr. Milton Shy and Dr. Glen Drager who described similar clinical symptoms in patients they were treating 1.
They documented a progressive disorder of the central and sympathetic nervous systems, characterized by multiple system atrophy that included an excessive drop in blood pressure, dizziness, constipation, impotence, urinary incontinence, impaired speech, anhidrosis, difficulties in breathing and swallowing, slowness in movement and speech, and other related symptoms 2.
What's in this Guide?
- What is Shy Drager Syndrome/MSA?
- Signs and Symptoms of Shy Drager Syndrome/MSA
- Differences Between Shy Drager Syndrome/MSA and Parkinson’s Disease
- What are the Causes of Shy Drager Syndrome/MSA?
- Is Shy Drager Syndrome/MSA Hereditary or Genetic?
- Diagnosis of Shy Drager Syndrome/MSA
- How is Shy Drager Syndrome/MSA Treated?
- Prognosis, End of Life Issues and Care for Shy Drager Syndrome/MSA Patients
- For more information on Shy Drager Syndrome/MSA
Disclaimer: Before You Read
It is important to know that your genes are not your destiny. There are various environmental and genetic factors working together to shape you. No matter your genetic makeup, maintain ideal blood pressure and glucose levels, avoid harmful alcohol intake, exercise regularly, get regular sleep. And for goodness sake, don't smoke.
Genetics is a quickly changing topic. Read More...
To acknowledge their contribution, this disorder was named Shy-Drager Syndrome.
Today, Shy-Drager Syndrome is now more commonly referred to as Multiple System Atrophy or MSA.
There are two main subtypes of MSA. These subtypes are characterized by the predominant symptom in each. Those two subtypes are MSA-predominant Parkinsonism (MSA-P) and MSA-predominant cerebellar ataxia (MSA-C).
People in all parts of the world are affected, with onset usually between ages 45 and 60. As many as 50,000 Americans have this disease 3, but diagnosis can be difficult because it can be confused with other similar disorders. Men are affected twice as frequently as women are.
The exact cause of the disease is not known, but medical professionals know it is not inherited and it is not contagious.
Dementia is not considered a common characteristic of MSA, but cognitive impairment does take place in some patients in the form of loss of verbal memory and verbal fluency.
There is no known cure for MSA, so managing symptoms are treated by the individual patient. Life expectancy after the onset of symptoms is currently about 6 to 10 years.
The Multiple System Atrophy (MSA) Coalition has developed a glossary of terms to help interested parties better understand the terminology related to MSA 4.
Signs and Symptoms of Shy Drager Syndrome/MSA
MSA-predominant Parkinsonism (MSA-P) is the most common form of MSA. The first signs and symptoms associated with MSA-P are similar to in a person with Parkinson’s disease, which is how it gets its name.
These symptoms may include:
- slowness or difficulty moving
- increased falls due to walking problems associated with shuffling of gait
- resting tremor (this usually disappears when a patient is moving and is more prominent at rest)
- slurred speech
- voice changes
- difficulty swallowing
- lack of facial expression
- a general clumsiness
MSA-predominant cerebellar ataxia (MSA-C) symptoms affect the cerebellum. The cerebellum plays an important role in synchronizing motor movement. Specifically, these symptoms can include:
- difficulty coordinating walking
- ataxia (problems with balance and coordination)
- hand movements
- eye movements
- a quavering voice
- bladder control problems, such as a sudden urge to urinate or difficulty emptying the bladder
At times, a person with MSA-C can appear to be intoxicated without having had an alcoholic beverages. For this reason, is may be advisable to carry a medical card to help explain a person’s actions if asked.
Other symptoms of both forms of MSA may include depression, anxiety, panic attacks, and suicidal thoughts partly due to the mental and emotional stresses associated with this complex disease.
Some patients may have inappropriate laughing or crying. Additionally, other symptoms in both forms may include:
- contractures (chronic shortening of muscles or tendons around joints, which prevents the joints from moving freely) in the hands or limbs
- Pisa syndrome, an abnormal posture in which the body appears to be leaning to one side like the Leaning Tower of Pisa
- antecollis, in which the neck bends forward and the head drops down
- involuntary, uncontrollable sighing or gasping
- sleep disorders, including a tendency to act out dreams (called REM/ (Rapid Eye Movement sleep behavior disorder)
Cognitive impairment may take place in up to 75% of patients. Dementia is thought to be rare in MSA but may affect 12% to 18% of patients 5.
A patient diagnosed with MSA-P may show symptoms of MSA-C, so these diagnoses are not always set in stone.
Differences in patterns of cognitive loss between MSA-P and MSA-C patients have also been noted. MSA-P patients tend to lose verbal memory while MSA-C patients show difficulty in acquiring new verbal information and maintaining attention.
MSA tends to progress more rapidly than Parkinson’s disease, and most people with MSA will require an aid for walking, such as a cane or walker, within a few years after symptoms begin.
One of the conditions associated with MSA is dysautonomia. This is a dysfunction of the autonomic nervous system and presents as problems regulating heart rate, blood pressure, breathing, digestion, and other internal organ functions.
With dysautonomia, patients may suffer from neurogenic orthostatic hypotension (NOH) which means they will become dizzy or faint when they sit up or stand up.
Conversely, blood pressure may be excessively high when lying down. Loss of bladder or bowel control, constipation, abnormal sweating, difficulty with heat, sexual impotence in men, and sleep disturbances are also common with dysautonomia.
Differences Between Shy Drager Syndrome/MSA and Parkinson’s Disease
To distinguish between MSA and Parkinson’s disease, it is useful to conduct what is known as a differential diagnosis.
A differential diagnosis is a way to evaluate a patient’s symptoms, list diseases that are likely to cause those symptoms and eliminate the ones that are less likely to be causing the patient’s current condition.
By eliminating less likely diseases, it’s possible to more readily diagnose MSA.
MSA is often mistaken for Parkinson’s disease because symptoms are similar in early stages. Parkinson’s is also a progressive neurodegenerative disorder that causes changes in motor and non-motor function.
Just like MSA, the key motor features are tremor, rigidity, reduced movement, and postural instability.
A resting tremor is also common in Parkinson’s as well. This may start in one side of the body, in the hands or feet. Hand tremors will appear as if the patient is rocking the hand back and forth. Resting tremors can also affect the lips, chin, jaw, and legs.
Rigidity is noted by increased resistance with passive motion.
Akinesia or bradykinesia is one of the most common features of Parkinson’s and involves difficulty in initiating movement tasks. This may show as speaking softly, decreased dexterity, reduced facial expression, and sleep disturbances.
Over time, individuals might begin to feel slow in their movement, difficulty initiating and repeating actions, and stiffness of the limbs and body.
Postural instability typically takes place later in Parkinson’s and can result in walking problems such as a freezing gait where a patient’s feet will get “stuck to the ground.” Many times, this leads to falls and hip fractures.
Postural instability is one of the defining clinical markers used to distinguish between Parkinson’s and MSA. The average time from the beginning of symptoms to a first fall is much longer in Parkinson’s.
Among the non-motor signs, which commonly occur before the motor signs, is a decrease or absence of sense of smell. Other symptoms include forgetfulness and slowness in thinking.
The diagnosis of Parkinson’s disease is made clinically and a diagnosis of MSA is not.
There are other conditions that are sometimes diagnosed as MSA. They include:
Pure autonomic failure is a diagnosis of involving the peripheral autonomic nervous system (ANS). The ANS is responsible for controlling blood pressure, sweating, urinary habits, and impotence.
Progressive supranuclear palsy (PSP) is a disorder similar to Parkinson’s. Patients present symptoms related to movement, falls, speech changes, difficulty swallowing, changes to vision, mood, and cognitive problems.
Some of the parts of the brain impacted by this disease include the frontal cortex and areas that control eye movements.
Dementia with Lewy bodies (DLB) is the third most common cause of dementia after Alzheimer’s disease and vascular dementia. This disease overlaps symptoms with Parkinson’s disease, such as rigidity, balance, and posture instability.
Symptoms of DLB include dysfunction of the autonomic nervous system, hallucinations, REM behavior sleep disorder, and memory changes.
Corticobasal degeneration initially shows symptoms of motor and/or cognitive difficulties. There may be problems with walking, limb rigidity, inability to perform purposeful movements, and speech problems.
Multiple sclerosis (MS) is an immune-related disorder. With MS, the body seems to mistake the brain for a pathogen. This disease predominately affects the spinal cord and brain.
Some early symptoms of MS are a temporary loss of vision or motor movement. Diagnosis is made clinically, and with an MRI scan.
Spinocerebellar ataxia is a genetic neurodegenerative disease that commonly occurs in individuals 30-50 years old. Early symptoms include poor coordination of gait, speech, and arms.
Diagnosis of spinocerebellar ataxia is determined by taking a family history and neurological evaluation. Medical imaging and genetic testing are also used to support the diagnosis.
What are the Causes of Shy Drager Syndrome/MSA?
The short answer is that nobody knows for sure. Most cases appear to be sporadic and random. However, a distinguishing feature of MSA is the accumulation of the protein alpha-synuclein in glia.
Glia are the cells that support nerve cells in the brain.
These deposits appear on a type of cell that makes myelin which is a coating on nerve cells that lets them conduct electrical signals rapidly.
This protein also accumulates in Parkinson’s disease, but in nerve cells.
A possible risk factor for the disease could also be variations in the synuclein gene SCNA, which provides instructions for the production of alpha-synuclein.
Is Shy Drager Syndrome/MSA Hereditary or Genetic?
MSA is considered a rare disease, similar in frequency to the more well-known neurodegenerative disease amyotrophic lateral sclerosis (ALS) or Lou Gehrig’s disease.
MSA has not traditionally been considered a genetic disease, but new evidence in recent years is supporting the idea that MSA may have some genetic predisposition in many patients.
Multiple system atrophy (MSA) is also not known to be an inherited condition, so a family history of a condition with similar symptoms may help your doctor either confirm or rule out MSA.
There are no objective or quantitative tests to reliably confirm a diagnosis in living patients.
The diagnosis in this disease is clinical, meaning that it is made based on history, examination, sometimes using supplementary information such as the results of an MRI of the brain, iodine-123-metaiodobenzylguanidine (MIBG) nuclear medicine scan, serum norepinephrine levels, or testing of the autonomic nervous system 6.
The only certain diagnosis is made by doing a brain autopsy, which shows accumulation of the protein α-synuclein within glial cells in the brain and degeneration of certain parts of the brain as well.
There are still many unknowns about this disease, but some of the recent advances made in MSA genetics may give important clues to understanding the pathogenesis and treatment of this disease.
The lack of specific confirmatory tests for the diagnosis of MSA, as well as the rarity of the disease have been major impediments that have made research in MSA difficult.
However, more attention has been given to the genetics of MSA recently and is starting to open new doors in the understanding of the pathogenesis of MSA.
Traditionally, most adult-onset neurodegenerative diseases have been considered sporadic rather than genetic in origin. But evidence is emerging that many neurodegenerative diseases may have not only pattern of inheritance, but also genes that strongly predispose to the condition.
\Examples of this include the ApoE gene for Alzheimer’s disease and GBA in Parkinson disease.
A large genome-wide association study is currently underway but few studies have attempted to analyze genetic predispositions in MSA. Genetics research in MSA is clearly lagging.
That said, some of the families described with SNCA mutations had members with a clinically consistent diagnosis of MSA. A few studies found significant associations between variants in the SNCA gene and sporadic cases of clinical MSA.
But MSA is not generally considered a genetic disease, and it has only rarely been described in families.
Research being done in MSA genetics have revealed several candidate genes that may be involved in the pathogenesis of the disease. The pathogenesis of MSA remains a mystery, though it is becoming clear that there are genetic associations to some degree.
While none of these genetic associations have a high confirmation for development of MSA, it does appear that they likely create a pre-disposition for this rare and devastating disease.
Diagnosis of Shy Drager Syndrome/MSA
Because MSA is similar to Parkinson’s in many ways, especially in the early stages, making a diagnosis of MSA challenging.
The other thing is that diagnosis of MSA can be challenging because there is no test that can make or confirm the diagnosis in a living patient.
True diagnosis can only be accomplished by examination of the brain post-mortem. As a result, some people are never properly diagnosed.
Typically, a doctor will take a medical history and perform a short neurological examination. This may be followed by a number of tests to help narrow down the diagnosis:
- These tests could include autonomic testing such as blood pressure or heart rate control. With a tilt table test, your blood pressure is monitored while you are on a special table that will tilt you to an almost upright position. This allows the physician to record blood pressure irregularities, and information about whether they occur with a change in physical position.
- Doctors may order other tests to assess your body's involuntary functions, such as a sweat test to evaluate perspiration or tests to assess your bladder and bowel function
- An MRI of the brain may identify changes that could indicate MSA or rule out other causes.
- A PET scan is sometimes used to see if metabolic function is reduced in specific parts of the brain.
- Electrocardiogram to track the electrical signals of the heart
- A DaTscan can assess the dopamine transporter in a part of the brain called the striatum. It can help a doctor determine if a condition is caused by a dopamine system disorder. The only drawback with this test is that it cannot differentiate between MSA and Parkinson’s disease.
- For patients with sleep irregularities, particularly if they involve interrupted breathing or snoring, physicians may recommend an evaluation in a sleep laboratory to determine if there is an underlying and treatable sleep disorder, such as sleep apnea.
- Individuals with MSA typically do not have sustained improvement in their symptoms with levodopa (a drug used to treat Parkinson’s disease), a finding that often supports the diagnosis of MSA.
- Pharmacological challenge tests which means that certain medications are given and then the patient’s body’s reaction to them is observed in controlled clinical settings
How is Shy Drager Syndrome/MSA Treated?
There's no cure for Shy Drager Syndrome/MSA. The best a patient can hope for is that the disease can be managed by treating signs and symptoms to make a patients as comfortable as possible by maintaining bodily functions.
In the early stages, MSA-P may respond to medications used for Parkinson’s disease. But MSA-P progresses more rapidly than Parkinson’s so after passing through initial stages, a patient will no longer respond to those medications.
Because symptoms and the time of progression varies widely, every individual course of treatment will also vary widely.
For example, some MSA patients will need assistance as early as five years after they are diagnosed, while others can live independently for as long as 20 years.
Doctors may prescribe treatments to counter specific symptoms of MSA. Those may include:
- Medications to raise blood pressure. This can include corticosteroid fludrocortisone, pyridostigmine (Mestinon), or Midodrine
- The FDA has also approved droxidopa (Northera) for treating orthostatic hypotension.
- Medications to reduce Parkinson's disease-like signs and symptoms. These can include a combination of levodopa and carbidopa (Duopa, Sinemet)
- A Pacemaker. A heart pacemaker may be installed to keep your heart beating at a rapid pace, to increase your blood pressure.
- Impotence drugs. Prescribed drugs can include sildenafil (Revatio, Viagra) to manage erectile dysfunction.
- Steps to manage swallowing and breathing difficulties including eating softer foods. If swallowing or breathing becomes increasingly problematic, a surgically inserted feeding or breathing tube may be inserted. In advanced MSA, you may require a tube (gastrostomy tube) that delivers food directly into your stomach.
- Bladder care. For problems early on medications may be prescribed. But in advanced stages, a catheter will be inserted permanently to allow you to drain your bladder.
- Physical and Speech Therapy. To maintain motor skills and speech for as long as possible.
Doctors will also advise self-care as well. This may include:
- Adding salt to your diet and drinking more fluids to raise blood pressure and volume.
- Elevating the head of your bed by 30 degrees to minimize blood pressure increases during sleep.
- Adding more fiber to a diet to ease constipation.
- Taking over-the-counter laxatives
- Staying in air-conditioned rooms and avoiding excessive heat.
- Wearing elastic support stockings up to your waist to keep your blood pressure from dropping.
Prognosis, End of Life Issues and Care for Shy Drager Syndrome/MSA Patients
While drugs, physical, speech and occupational therapies can help keep muscles strong and flexible, many patients succumb to secondary conditions of MSA.
These can include pulmonary embolisms, blood clots in an artery that travels to the lungs, pneumonia from aspirating food or saliva into the bronchial tubes.
Sleep apnea and problems regulating blood pressure are also common contributing factors to a patient passing away.
Urinary tract infections due to disorders of the bladder can progress to overwhelming sepsis and lead to death.
Many patients develop laryngeal stridor and difficulty swallowing, which can also lead to pneumonia. In addition, many patients with MSA experience Cheyne-Stokes or periodic respiration.
In some cases, this may lead to a critical loss of respiratory drive called Ondine's curse.
The prognosis for MSA patients is that most will pass away from the disease or related complications within 6-10 years after the onset of symptoms. It is rare for a patient to survive 10 years.
However, advancements in research in Parkinson’s disease progresses, so do advancements in research in MSA.
This is because the neurobiology of MSA may be related to other neurodegenerative diseases like Parkinson’s disease. So, when advancements are made in other diseases, it may also benefit MSA patients as well.
Much of this research is being conducted by the National Institute of Neurological Disorders and Stroke (NINDS). NINDS’s mission is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease.
NINDS is a part of the National Institutes of Health (NIH), the leading supporter of biomedical research in the world. Both institutes support research on multiple system atrophy and related disorders.
MSA is one of the diseases being studied as part of the NINDS Parkinson’s Disease Biomarkers Program. This major NINDS initiative is aimed at discovering ways to identify individuals at risk for developing Parkinson’s disease and related disorders and to track the progression of the disease
More research on neurodegenerative diseases such as MSA can be found through the NIH RePORTER, a searchable database of current and past research projects supported by NIH and some other federal agencies.
For more information on Shy Drager Syndrome/MSA
For more information on neurological disorders or research programs funded by the National Institute of Neurological Disorders and Stroke, contact the Institute's Brain Resources and Information Network (BRAIN) at:
P.O. Box 5801
Bethesda, MD 20824
Information also is available from the following organizations:
National Library of Medicine (NLM)
National Institutes of Health, DHHS
8600 Rockville Pike, Bldg. 38, Rm. 2S10
Bethesda, MD 20894
Tel: 301-496-6308; 888-346-3656
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- The History of Multiple System Atrophy (Formerly Shy-Drager Syndrome (SDS). The Multiple System Atrophy Coalition. Retrieved Online, June 2019.
- Medical Definition of Shy-Drager syndrome.
William C. Shiel Jr., MD, FACP, FACR. MedicineNet. 2017.
- Multiple System Atrophy Fact Sheet.
National Institute of Neurological Disorders and Stroke. Retrieved online, 2019.
- MSA Glossary.
The Multiple System Atrophy Coalition. Retrieved online 2019.
- Multiple System Atrophy: What You Need to Know.
Daniel Claassen, MD, Allyson Mayeux, MD, and Annette Hoy, MD. The MSA Coalition. April 4, 2019.
- UNDERSTANDING MULTIPLE SYSTEM ATROPHY— COULD GENETICS LEAD THE WAY?
Miriam Sklerov, Cheryl Waters. 2016.