Multiple System Atrophy (MSA)

What multiple system atrophy is

MSA gets its name because it damages several systems in the brain at once. Clumps of a protein called alpha-synuclein build up inside oligodendrocytes, the support cells that make the insulating sheath around nerves. Nerve cells in the basal ganglia, cerebellum, brainstem and spinal cord then shrink (atrophy) and die.

Alpha-synuclein is the same protein involved in Parkinson's disease and Lewy body dementia, but in those it collects inside nerve cells rather than support cells. The cause of MSA is unknown. It is not usually inherited and does not run in families.

Older names, now retired, described the different presentations: Shy-Drager syndrome (prominent autonomic failure), striatonigral degeneration (Parkinson-like) and olivopontocerebellar atrophy (cerebellar).

Types of MSA

Over time, most people develop features of both types, along with autonomic failure.

Symptoms of multiple system atrophy

Autonomic symptoms

These often appear first, sometimes years before movement problems:

• Orthostatic hypotension: a drop in blood pressure on standing, causing dizziness, blurred vision, neck and shoulder ache ("coat hanger" pain) or fainting. Often worse after meals, in heat and in the morning.
• Bladder problems: urgency, frequency, incontinence and incomplete emptying.
• Erectile dysfunction in men, often an early sign.
• Constipation.
• Reduced sweating and intolerance of heat, and cold, purple hands and feet.

Movement symptoms

• slowness and stiffness, with or without tremor
• poor balance and early falls
• clumsiness, unsteady gait and slurred speech (in MSA-C)
• a forward-bent neck (antecollis) or leaning to one side
• curled fingers or toes (dystonia)

Sleep and breathing symptoms

• REM sleep behavior disorder: acting out dreams, which often appears years before diagnosis. See REM sleep behavior disorder.
• Stridor: a high-pitched noise when breathing in, from weakness of the vocal cords, especially at night. It can be dangerous.
• sleep apnea and snoring

Other symptoms

• swallowing difficulty and choking
• a quiet, strained or shaky voice
• emotional changes such as uncontrollable laughing or crying
• depression and anxiety

Thinking and memory are usually relatively preserved, though slowed thinking and difficulty with planning can occur.

MSA vs Parkinson's disease and PSP

Diagnosis

There is no single definitive test while a person is alive. A neurologist diagnoses MSA from the pattern of symptoms using the Movement Disorder Society criteria, and supporting tests:

• Lying and standing blood pressure, or a tilt-table test. A sustained drop of 20 mmHg systolic or more (30 mmHg in the 2022 criteria for established MSA) supports the diagnosis.
• Bladder scan after urinating, to measure retained urine, and urodynamic studies.
• Brain MRI: may show shrinkage of the putamen, pons or cerebellum, or a "hot cross bun" pattern in the pons.
• DaTscan or other nuclear imaging: shows dopamine loss but does not separate MSA from Parkinson's on its own.
• Sleep study for REM sleep behavior disorder, stridor and sleep apnea.
• Levodopa trial: a poor response points toward MSA.
• Emerging tests: skin biopsy and spinal fluid tests for abnormal alpha-synuclein are being used in some centers.

Treatment

No treatment yet slows MSA. Care focuses on symptoms and safety, ideally through a team including a neurologist, nurse specialist, physical, occupational and speech therapists, a urologist and palliative care.

Low blood pressure on standing

• Stand up slowly, sit on the edge of the bed first, and avoid standing still for long.
• Drink about 2 to 2.5 liters of fluid a day and increase salt if your doctor agrees.
• Eat smaller meals and limit alcohol.
• Use waist-high compression stockings or an abdominal binder.
• Sleep with the head of the bed raised about 10 to 20 degrees, which also limits high blood pressure lying down.
• Medicines such as midodrine, fludrocortisone, droxidopa or pyridostigmine may be prescribed.

Movement

• A trial of levodopa, which helps some people with MSA-P, at least for a while.
• Physical therapy for balance, walking aids and fall prevention.
• Botulinum toxin injections for painful dystonia.

Bladder and bowel

• Medicines for urgency, chosen carefully because some worsen confusion or retention.
• Intermittent self-catheterization or a long-term catheter for incomplete emptying.
• Fiber, fluids and laxatives for constipation.

Breathing, swallowing and speech

• CPAP at night for stridor or sleep apnea. Some people need a tracheostomy.
• Speech and language therapy, modified diets and, if swallowing becomes unsafe, a feeding tube.

Sleep and mood

Melatonin or clonazepam for REM sleep behavior disorder, and treatment for depression and anxiety.

Outlook

MSA progresses steadily. Many people need a walking aid within about 3 to 5 years of symptom onset and a wheelchair a few years later. Average survival from first symptoms is about 6 to 10 years, though some people live considerably longer. Common causes of death are chest infections, breathing problems during sleep and sudden death. Advance care planning early, while speech is clear, helps people make their wishes known.

Frequently asked questions

What is the life expectancy with multiple system atrophy?

On average, people live about 6 to 10 years after symptoms begin, but the range is wide and some live 15 years or more. Faster progression is linked to early, severe autonomic failure. Good management of breathing, swallowing and falls can help.

How is MSA different from Parkinson's disease?

MSA usually causes early and severe autonomic problems such as fainting on standing and bladder failure, responds poorly to levodopa, and progresses faster. Parkinson's disease typically responds well to levodopa for years, with autonomic problems appearing later and more mildly.

Is multiple system atrophy hereditary?

Almost never. MSA occurs sporadically, and family members do not have a meaningfully higher risk. Very rare family clusters have been described, but genetic testing is not part of routine care.

What are the first signs of MSA?

Early signs often include erectile dysfunction, bladder urgency or incontinence, dizziness on standing and acting out dreams in sleep. These can appear months or years before slowness, stiffness or unsteadiness lead to a diagnosis.

Is there a cure for MSA?

Not yet. Treatments can ease low blood pressure, bladder symptoms, stiffness, sleep and breathing problems, and therapy helps maintain independence. Clinical trials are testing drugs that target alpha-synuclein.