Multiple system atrophy

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Multiple system atrophy is a progressive brain disorder that affects movement and balance and disrupts the function of the autonomic nervous system. The autonomic nervous system controls body functions that are mostly involuntary, such as regulation of blood pressure. The most frequent autonomic symptoms associated with multiple system atrophy are a sudden drop in blood pressure upon standing (orthostatic hypotension), urinary difficulties, and erectile dysfunction in men.

Researchers have described two major types of multiple system atrophy, which are distinguished by their major signs and symptoms at the time of diagnosis. In one type, known as MSA-P, a group of movement abnormalities called parkinsonism are predominant. These abnormalities include unusually slow movement (bradykinesia), muscle rigidity, tremors, and an inability to hold the body upright and balanced (postural instability). The other type of multiple system atrophy, known as MSA-C, is characterized by cerebellar ataxia, which causes problems with coordination and balance. This form of the condition can also include speech difficulties (dysarthria) and problems controlling eye movement.

Multiple system atrophy usually occurs in older adults; on average, signs and symptoms appear around age 55. The condition worsens with time, and affected individuals survive an average of 10 years after the signs and symptoms first appear.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Multiple system atrophy is a complex condition that is likely caused by the interaction of multiple genetic, environmental, and lifestyle factors. Some of these factors have been identified, but many remain unknown.

Changes in several genes are being studied as possible risk factors for multiple system atrophy. The genetic risk factors with the most evidence are variants in the SNCA and COQ2 genes. The SNCA gene provides instructions for making a protein called alpha-synuclein, which is abundant in normal brain cells but whose function is unknown. Studies suggest that several common variations in the SNCA gene are associated with an increased risk of multiple system atrophy in people of European descent. It is unclear whether these variations also affect disease risk in other populations. The COQ2 gene provides instructions for making a protein called coenzyme Q2. This enzyme carries out one step in the production of a molecule called coenzyme Q10, which has a critical role in energy production within cells. Variations in the COQ2 gene have been associated with multiple system atrophy in people of Japanese descent, but this association has not been found in other populations. It is unclear how changes in the SNCA or COQ2 gene increase the risk of developing multiple system atrophy.

Researchers have also examined environmental factors that could contribute to the risk of multiple system atrophy. Initial studies suggested that exposure to solvents, certain types of plastic or metal, and other potential toxins might be associated with the condition. However, these associations have not been confirmed.

In all cases, multiple system atrophy is characterized by clumps of abnormal alpha-synuclein protein that, for unknown reasons, build up in cells in many parts of the brain and spinal cord. Over time, these clumps (which are known as inclusions) damage cells in parts of the nervous system that control movement, balance and coordination, and autonomic functioning. The progressive loss of cells in these regions underlies the major features of multiple system atrophy.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Most cases of multiple system atrophy are sporadic, which means they occur in people with no history of the disorder in their family. Rarely, the condition has been reported to run in families; however, it usually does not have a clear pattern of inheritance.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Multiple system atrophy has a prevalence of 2 to 5 per 100,000 people.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal autonomic nervous system physiology · Frequent (79-30%)

A functional abnormality of the autonomic nervous system.

Abnormal brain FDG positron emission tomography · Frequent (79-30%)

An anomaly detectable in [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) brain scans. Glucose uptake measured with FDG-PET is a marker of neuronal metabolic activity.

Abnormal pyramidal sign · Frequent (79-30%)

Functional neurological abnormalities related to dysfunction of the pyramidal tract.

Abnormal rapid eye movement sleep · Frequent (79-30%)

Abnormality of REM Sleep are phases of REM sleep are characterized by desynchronized EEG patterns, increases in heart rate and blood pressure, sympathetic activation, and a profound loss of muscle tone except for the eye and middle-ear muscles. There are also phases of rapid eye movements.

Autonomic bladder dysfunction · Frequent (79-30%)

Abnormal bladder function (increased urge or frequency of urination or urge incontinence) resulting from abnormal functioning of the autonomic nervous system.

Autonomic erectile dysfunction · Frequent (79-30%)

Impotence (inability to develop or maintain an erection) resulting from abnormal functioning of the autonomic nervous system.

Axial dystonia · Frequent (79-30%)

A type of dystonia that affects the midline muscles, i.e., the chest, abdominal, and back muscles.

Bradykinesia · Frequent (79-30%)

Bradykinesia literally means slow movement, and is used clinically to denote a slowness in the execution of movement (in contrast to hypokinesia, which is used to refer to slowness in the initiation of movement).

Other findings in the same source

From: Orphanet

Additional reported features include Camptocormia (Frequent (79-30%)); Central sleep apnea (Frequent (79-30%)); Constipation (Frequent (79-30%)); Dysarthria (Frequent (79-30%)); Female anorgasmia (Frequent (79-30%)); Gait ataxia (Frequent (79-30%)); Gaze-evoked nystagmus (Frequent (79-30%)); Orthostatic syncope (Frequent (79-30%)); Parkinsonism (Frequent (79-30%)); Postural instability (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Multiple system atrophy is Neurology, with a neurologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which nervous-system findings help explain the symptoms?
• Would an assessment of walking, communication or daily function be helpful?
• Are rehabilitation or other specialist services relevant?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Multiple system atrophy. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.