Multiple System Atrophy (MSA)

Multiple system atrophy (MSA) is a slowly progressive neurodegenerative disease that afflicts approximately 25,000-75,000 Americans, with approximately 10,000 new cases diagnosed each year. MSA has a higher prevalence than that estimated due to the difficultly in differentiating it from other disorders causing many patients to not receive the correct diagnosis during their lifetime.


MSA is one of the parkinsonian disorders that is preceded by significant non-motor symptoms characterized by autonomic failure and sleep disturbances.

Non-motor symptoms
The autonomic nervous system is the body’s internal system that controls most of the involuntary functions of the body. Examples of this include: controlling urinary bladder function, maintaining the blood pressure, and controlling breathing, heart beating and bowel motion. The failure of the function of this system is called “dysautonomia”. 

Studies have shown that blood pressure, urinary bladder and genital organs are affected early by MSA. The autonomic nervous system normally works to increase blood pressure when standing up quickly from a sitting or lying position to maintain blood supply to the brain, but orthostatic hypotension occurs when the autonomic system fails. It can result in feeling about to faint, fatigue, tiredness or a syncopal event. The main danger is the risk of fall and fall related consequences.

Other examples of dysautonomia affecting the urinary bladder include: increased urinary frequency, urinary urgency, and feeling of incomplete urinary bladder emptying. The inability to maintain erection during sexual intercourse or losing morning erection could also occur as early manifestation of the disease.

Sleep disorders in MSA include Rapid eye movement sleep Behavior Disorder (RBD), fragmented sleep, restless leg syndrome (RLS), and excessive daytime sleepiness. RBD is the most common among these symptoms, which usually precedes motor symptoms or may occur with its onset. It involves abnormal behavior during the sleep phase with Rapid Eye Movement (REM sleep) in which the content of the dreams can be vivid, violent, and frightening and patients may act out their dreams. Obstructive sleep apnea (OSA), a frequent cessation of breath during sleep, may also occur. 

Motor symptoms
MSA is one of the atypical parkinsonian syndromes. As in Parkinson’s disease, MSA is characterized by slowness of movement that may lead to an increase in the amount of time needed to accomplish the activities of daily living (bradykinesia), decrease in amplitude of movement that may lead to decrease associated movements when walking, lower tone of voice (hypophonia), and stiffness of the muscles (rigidity). People with MSA may develop tremor, clumsiness, early shuffling gait, and frequent falls.

Patients with MSA may develop "axial" dystonia that affects mostly the neck and trunk of the body that can lead to limitation of movement, odd postures (torticollis, particularly forward: antercollis) and occasionally, to pain. In addition to axial dystonia, they may have dystonia of the vocal cords that manifest as a stridor, an easily recognizable harsh and strained high-pitched sound that occurs when breaking in and cannot be confused with regular snoring even if it is heavy. 

At times patients with MSA may present with "cerebellar" features characterized by ataxia (a broad-base gait), poor balance as well as impaired movement coordination that can interfere with the fine tuning of muscular movement and result in coarse, jerky, uncoordinated movements.

Cognitive function in MSA tends to be relatively well preserved but usually patients exhibit frontal disturbances (difficulties planning, multitasking, decreased fluency). Mood is more significantly affected in MSA patients, with high rates of depression and anxiety.

There are two main forms of MSA: the one in which parkinsonism predominates, MSA-P; and the one in which cerebellar features predominate, MSA-C. Both have similar survival, but the MSA-P may more greatly affect quality of life. Commonly, patients may end up having both parkinsonism and cerebellar features.


Although the cause of MSA is currently unknown, there is evidence that the primary defect occur in glial cells, a type of cells in the nervous system that function to provide support and protection for neurons in the brain, and maintain physiological balance. Abnormal aggregation of multiple types of protein mainly a protein called alpha-synuclein (and others like tau and ubiquitin) in glial cells lead these cells to malfunction or die. The alpha-synuclein aggregates from the "glial inclusions" in MSA. 

Alpha-synuclein also abnormally aggregates in Parkinson's disease, but in Parkinson's disease the aggregates are mostly located in neurons forming the "Lewy bodies."


Treatments effective for disease modification or neuroprotection are not available for MSA today. The management of the disease is aimed at controlling and alleviating symptoms of the disease, avoiding complications, which in turn improve the quality of the patient’s life.

A multidisciplinary management approach is important for MSA. Along with a movement disorder specialist, urologist, physical, speech, and occupational therapists and dietitians should be involved in the management plan.


For orthostatic hypotension, measures can be taken to prevent it including: rising slowly from supine to sitting position, raising the head of the bed 20 to 30 degrees with a furniture raiser, and increasing daily salt and water intake. Using custom-fitted elastic stockings that extend to the waist or readjusting medication can help maintain blood pressure and prevent significant drops. Abdominal bands are also beneficial. 

When these measures are insufficient, medications such as fludrocortisone that retain salt, or midodrine that increase the blood pressure may be needed. Management of the orthostatic hypotension includes taking the blood pressure lying and standing to avoid the complications of having hypertension when lying down.

Bladder function should be evaluated by a urologist, usually requiring a urodynamic study that allows the physician to better manage the "neurogenic bladder." If the bladder tends to be hyperactive with increased frequency of urination, medications (such as oxybutynin and tolterodine) can help to decrease frequency and urgency symptoms and improve bladder control. These medications should be used with caution of developing side effects like confusion or worsening constipation. If the bladder is hypotonic, other medications need to be used. It is also important to know whether any of these abnormalities associate with hypertrophic prostate. The surgical treatment of the latter is not too successful in MSA. Moreover, certain medications used to treat the hypertrophic bladder such as tamsulosin, may worsen the orthostatic hypotension.

Sleep and breathing disorders
REM sleep behavioral disorder symptoms can be treated by melatonin, a natural hormone in the human body that is available over the counter. When melatonin is not effective, other therapies could be tried such as gabapentin or clonazepam.

To improve the obstructive sleep apnea, a machine that provides positive pressure ventilation with either a Continuous Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure (BiPAP) system may be needed.

Motor symptoms
In at least one-third of the patients, the parkinsonism may improve with antiparkinsonian medications. The best treatment is carbidopa-levodopa or other formulations of levodopa. Dopaminergic agonists such as pramipexole, ropinirol, or rotigotine are not as effective and may worsen the orthostatic hypotension.

Physical therapy is also very important to prevent falls and maintain and improve gait. The physical therapist helps to determine the best walking aid when needed. A cane or a weighted walker with laser light may be very useful when there is freezing. Special programs like LSVT-BIG can result in a significant improvement in motor symptoms. 

U-Step Weighted Walker

Dystonia may improve with botulinum toxin injections, usually administered by the movement disorder specialist. Stridor may benefit from botulinum toxin injections, but at times is so severe that it may require a tracheostomy. 

Speech therapists play an important role in assessing the speech and swallowing functions. LSVT-LOUD may be useful to improve voice projection and speech quality. A modified barium swallowing test helps determine if patients can tolerate all types of consistencies of food by checking with a small quantity of barium if food goes to the food-tube. If food goes instead to the air-tube, it could cause choking or lung infections. Increasing the consistency of the food, changing the position of the head when eating, or at times percutaneous endoscopic gastronomy tubes may be needed to improve the swallowing disturbances.

Occupational therapists help to improve the patient’s performance of the activities of daily living, thus promoting longer independence and better quality of life.

MSA is a disabling disease in it’s advanced stage. Social support through local, regional, and national associations can play an integral role in improving the lives of patients, family members, and caregivers. 

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