Department of Neurology

Multiple System Atrophy (MSA)

What is Multiple System Atrophy (MSA)?

MSA refers to a group of progressive neurodegenerative disorders, previously referred to as Shy-Drager syndrome, striatonigral degeneration, and olivoponto¬cerebellar atrophy. Shy-Drager syndrome was named after the two physicians who first described it in 1960: Dr. Milton Shy from the National Institutes of Health and Dr. Glenn Drager from Baylor College of Medicine. For various reasons the eponym Shy-Drager syndrome has been replaced by MSA. The two cardinal features of MSA are dysautonomia and atypical parkinsonism. Dysautonomia refers to a disturbance of the autonomic nervous system, the nerve pathways which regulate unconscious bodily functions including heart rate, blood pressure, digestion, salivation, perspiration, micturition (release of urine), and some sexual functions. The features of parkinsonism, are those shared with Parkinson's disease, specifically muscle stiffness (rigidity), slowness of movement (bradykinesia), stooped posture, and impaired balance. A tremor while at rest may also occur in both MSA and Parkinson's disease but is more common in the latter. In any given individual, the diagnosis of MSA is typically followed with the letter A, P or C to denote whether autonomic, parkinsonian or cerebellar features are most prominent.

What are typical symptoms and signs of dysautonomia (MSA-A)?

Patients with dysautonomia often experience symptoms of fainting or dizziness upon changing to a more upright position (such as standing up). The lightheadedness results from a drop in blood pressure that occurs upon standing, which in turn decreases the amount of blood returning to the brain. When a patient collapses to the floor, the amount of blood reaching the brain increases as the blood pressure rises, and the patient regains consciousness. Other typical symptoms of autonomic nervous system dysfunction are constipation, loss of erectile function in males (impotence), and loss of bladder or bowel control leading to urinary retention or involuntary urination or defecation (incontinence). Some patients experience abnormal sweating and develop bluish-purplish discoloration of skin (known as "the cold hand or cold foot sign"). MSA patients also frequently snore during sleep, have longer than normal pauses in breathing during sleep (sleep apnea), and exhibit combative behavior during sleep, known as REM Behavioral Disorder (RBD).

What are typical symptoms and signs of parkinsonism (MSA-P)?

The parkinsonian features of MSA typically include slowed and shuffling gait, difficulty with balance, stiffness (rigidity) of muscles, particularly those involving the neck, and slurred and low-volume speech. Neck and trunk muscle rigidity or weakness may result in abnormal postures such as forward bending of the neck (anterocollis) or a body tilt when sitting ("pisa sign"). Tremor, if present, is usually mild. Patients also may develop hoarseness, difficulty breathing from vocal cord weakness, and frequent involuntary sighing.

MSA-P is more common in men than women, usually presenting in one's late 40's or early 50's. Initial symptoms of MSA overlap with those of Parkinson's disease, and many patients initially respond to the same medications used for Parkinson's disease. As a result, most patients with MSA are first diagnosed with classic Parkinson's disease. The course of the MSA-P varies markedly from one individual to another; while some patients live for up to 20 years after the onset of symptoms, most patients reach severe disability, requiring assistance with waking (ambulation) and with activities of daily living within 5-8 years.

What are typical symptoms and signs of cerebellar dysfunction (MSA-C)?

MSA-C is characterized by poor coordination and progressive loss of balance (ataxia). In addition, patients with MSA-C may have "action" tremor, which is different from the "resting" tremor seen in typical Parkinson's disease. This tremor is present during activities, such as reaching for objects or when eating, and can be elicited on examination by the finger-to-nose maneuver. Other features include slurring of speech, difficulty with swallowing, and progressive weakness. Dysautonomia, while it may be present, is usually not a prominent feature of MSA-C. In contrast to MSA-P, MSA-C occurs with equal frequency in men and women. Age at onset ranges from the early 20's to the 60's. The first symptom is usually mild incoordination in one's hands and legs, eventually progressing to loss of balance requiring a walker or a wheelchair.

How is MSA diagnosed?

There is no diagnostic test for MSA, but a neurologist usually suspects the diagnosis based on a patient's physical examination and clinical course. Early in the disease, it can be challenging to differentiate MSA-P from Parkinson's disease, but evidence of autonomic nervous system dysfunction helps make this distinction. MSA-C may be confused with inherited forms of cerebellar ataxia if a careful family history is not elicited.

In MSA-P, brain MRI scans, may demonstrate abnormal signal in the putamen (a cluster of cells deep in the brain involved in regulating movement). In cases of MSA-C, MRI shows shrinkage (atrophy) of the cerebellum and brainstem. Brain scans, however, cannot not always distinguish MSA from similar neurodegenerative diseases. Also, because MSA is a rare condition, these characteristic changes are sometimes not recognized by radiologists; therefore, the scans should be examined by a neurologist experienced in the diagnosis of MSA.

Diagnosis of MSA may also be aided by testing the autonomic nervous system, for example, by measuring blood pressure and heart rate with the patient lying down compared with standing up. A drop in blood pressure while standing (orthostatic hypotension) is suggestive of autonomic dysfunction. A sleep study (polysomnogram) can document sleep apnea (pauses in breathing during sleep). In some cases the diagnosis of MSA cannot be confirmed until an autopsy examination of the brain is performed, which usually shows "glial cytoplasmic inclusion bodies" (protein aggregations within nerve cells) and other characteristic abnormalities.

What causes MSA?

Despite intensive research, the cause of MSA is still unknown. There is little evidence that MSA is a genetic disorder, as most persons with MSA have no family history of neurological disease. The pathological findings of MSA are distinct from Parkinson's disease; however, studies suggest that there may be an overlap between these two disorders in terms of the process of neurodegeneration. Like those with Parkinson's disease, patients with MSA accumulate the protein α-synuclein within specific brain cells. Why this protein is mishandled and how that results in nerve cell damage remains an area of intense interest among neuropathologists and neuroscientists. Abnormalities with the SNCA (alpha synuclein gene) have been found to increase the risk of developing MSA. MSA-C has also been reported to be rarely caused by the gene for another disorder of coordination, namely spinocerebellar ataxia (SCA3).

How is MSA treated?

In the early stages of MSA, levodopa and drugs that act directly on dopamine receptors (dopamine agonists) may lessen parkinsonian symptoms, such as slowness of movement. On average, however, these drugs are less effective in patients with MSA compared to those with Parkinson's disease. Also, many patients with MSA develop involuntary movements (dyskinesias), particularly involving their face, after prolonged levodopa use. Levodopa may also lower blood pressure, which is problematic for patients with autonomic dysfunction.

For patients with autonomic dysfunction, there are treatments that lessen the drop in blood pressure when upright. These treatments include increasing the amount of salt in the diet, fludrocortisone (a steroid hormone), midodrine and pyridostigmine (drugs that stimulate the autonomic nervous system), and the daytime use of support hose such as Jobst stockings to decrease pooling of blood in the legs. Because these methods can increase blood pressure to undesirably high levels when the patient is lying down, the head of the patient's bed should be elevated at least 30 degrees. Continuous Positive Airway Pressure (CPAP) breathing machines at night may be helpful for those patients with MSA who have documented sleep apnea. Increased urinary frequency due to an overactive bladder usually improves with solifenacin (VESIcare), tolterodine (Detrol) or similar medications. Sildenafil (Viagra) and related drugs may be effective for erectile dysfunction but can unmask dizziness (orthostatic hypotension) and should be used with caution. Urological consultation is recommended in most cases of MSA. Because of swallowing problems some patients require placement of a feeding tube (PEG) directly into the stomach in order to maintain adequate nutrition and prevent aspiration pneumonia.

Non-drug treatments for MSA include physical therapy and stretching exercises designed to maintain strength and flexibility. Devices which make walking safer, such as a walker, can also be helpful. At present, there are no therapies that can reverse or even retard the progression of MSA. Furthermore, since MSA is rare, clinical drug trials are sometimes not available for affected patients. Nonetheless, there is reason for hope. Because the biology of MSA may be related to other neurodegenerative diseases, like Parkinson's disease, it is possible that therapies designed for other conditions will also prove helpful for patients with MSA.

Selected References

Appendix

SDS/MSA Support Group

http://www.shy-drager.com/news.htm
http://www.msaweb.co.uk
http://groups.yahoo.com/group/shydrager
http://www.emedicine.com/neuro/topic671.htm
http://www.wemove.org

For additional information visit http://www.bcm.edu/neurology/pdcmdc/

• Home
• Patients & Visitors
  • Overview
  • Patient Education
  • Maps & Directions
  • Find a BCM Neurology Provider
  • Authorization for Release of Protected Health Information
• Clinical Programs
  • Autonomic Function
  • EMG/NCV
  • Epilepsy/
    Neurophysiology
  • Medical Neuromuscular
  • Memory & Dementia
  • Multiple Sclerosis
  • Neurogenetics
  • Parkinson’s & Movement Disorders
  • Vascular Neurology
• Research Programs
  • Neurobiology
  • Neuroimmunology
  • Parkinson’s & Movement Disorders
• Education
  • Overview
  • Note from the Program Director
  • BCM
    Medical Students
  • National & International Students
  • Residency in
    Adult Neurology
  • Residency in
    Pediatric Neurology
  • Poster Presentations
  • Clinical & Research Fellowships
  • Current Residents and Fellows
  • Application Process
  • Clinical Neuroscience
    Grand Rounds
  • Neurology
    Lecture Series*
  • Case of the Month
• Faculty
  • Neurology
  • Pediatric Neurology
  • Adjunct/Voluntary
  • Publications
  • Poster Presentations
  • Activities
  • Recruitment
• Calendar
  • Seminars & Rounds
  • Administration*
  • On-Call Schedule*
  • News & Events
• About Us
  • Neurology Yearbook
  • Texas Medical Center
• Help Us
  In Our Mission
• Links & Resources
• Resources
  *(BCM login required)
• Contact Us
  • Contact Neurology
  • Baylor Secure Messaging
  • BIGFILE Upload
• Site Map