Multiple system atrophy

Synonyms

1

Overview

Multiple system atrophy (MSA) is a degenerative neurological disorder. MSA is associated with the degeneration of nerve cells in specific areas of the brain. This cell degeneration causes problems with movement, balance, and autonomic functions of the body such as bladder control or blood-pressure regulation. The cause of MSA is not conclusively known and no specific risk factors have been identified, although research indicates that a prion form of the alpha-synuclein protein may be the cause of the disease. Around 55% of cases occur in men, with typical age of onset in the late 50s to early 60s. MSA often presents with some of the same symptoms as Parkinson's disease. However, MSA patients generally show minimal if any response to the dopamine medications used for Parkinson's. MSA is distinct from the more common syndrome multisystem proteinopathy. It should also not be confused with the two terms multiple organ dysfunction syndrome or multiple organ system dysfunction syndrome, which are the more modern and accurate terms for multiple organ failure or multiple organ system failure, which is an often-fatal complication of septic shock (due to severe sepsis, a systemic infection that has spread to the bloodstream) or other very severe illnesses or injuries.

Symptoms

MSA is characterized by a combination of the following, which can be present in any combination: Because people with MSA often experience "akinetic-rigid syndrome" (i.e. slowness of initiation of movement resembling Parkinson's disease) found in 62% at first presentation it is sometimes grouped with diseases referred to as Parkinson plus syndrome.

  • autonomic dysfunction
  • parkinsonism (muscle rigidity +/ tremor and slow movement)
  • ataxia (Poor coordination / unsteady walking)

When autonomic failure predominates, the term Shy–Drager syndrome is sometimes used, although this term is no longer current, given the terminology changes which are explained below.

A variant with combined features of MSA and Lewy body dementia may also exist.

Initial presentation

The most common first sign of MSA is the appearance of an "akinetic-rigid syndrome" (i.e. slowness of initiation of movement resembling Parkinson's disease) found in 62% at first presentation. Other common signs at onset include problems with balance (cerebellar ataxia) found in 22% at first presentation, followed by genito-urinary problems (9%). For men, the first sign can be erectile dysfunction (inability to achieve or sustain an erection). Women have also reported reduced genital sensitivity. Both men and women often experience problems with their bladders including urgency, frequency, incomplete bladder emptying, or an inability to pass urine (retention). About 1 in 5 MSA patients will fall in their first year of disease.

Progression

As the disease progresses one of three groups of symptoms predominate. These are:

  1. Parkinsonism (slow, stiff movement, writing becomes small and spidery)
  2. Cerebellar dysfunction (difficulty coordinating movement and balance)
  3. Autonomic nervous system dysfunction (impaired automatic body functions) including:
  • postural or orthostatic hypotension, resulting in dizziness or fainting upon standing up
  • urinary incontinence or urinary retention
  • impotence
  • constipation
  • vocal cord paralysis
  • dry mouth and skin
  • trouble regulating body temperature due to sweating deficiency in all parts of the body
  • loud snoring, abnormal breathing or inspiratory stridor during sleep
  • other sleep disorders including sleep apnea, REM Behavior Disorder

Other symptoms such as double vision can occur. Not all patients experience all of these symptoms.

Some patients (20% in one study) experience significant cognitive impairment as a result of MSA

Causes

There's no known cause for brain changes in multiple system atrophy (MSA). Some researchers are studying whether there's an inherited component or environmental toxin involved in the disease process, but there's no substantial evidence to support these theories.

MSA is associated with deterioration and shrinkage (atrophy) of portions of your brain (cerebellum, basal ganglia and brainstem) that regulate internal body functions, digestion and motor control.

Evaluation under a microscope of damaged brain tissue of people with MSA reveals nerve cells (neurons) that contain an abnormal amount of a protein called alpha-synuclein. Some research suggests that this protein may be overexpressed in multiple system atrophy.

Prevention

Currently, Multiple system atrophy cannot be prevented.

Diagnosis

Diagnosis of MSA can be challenging because there is no test that can definitively make or confirm the diagnosis in a living patient. Clinical diagnostic criteria were defined in 1998 and updated in 2007. Certain signs and symptoms of MSA also occur with other disorders, such as Parkinson's disease, making the diagnosis more difficult.

A definitive diagnosis can only be made pathologically on finding abundant glial cytoplasmic inclusions in the central nervous system.

Prognosis

MSA usually progresses more quickly than Parkinson's disease.[32] There is no remission from the disease. The average remaining lifespan after the onset of symptoms in patients with MSA is 7.9 years.[32] Almost 80% of patients are disabled within five years of onset of the motor symptoms, and only 20% survive past 12 years.[33] Rate of progression differs in every case and speed of decline may vary widely in individual patients.

O’Sullivan and colleagues (2008) identified early autonomic dysfunction to be the most important early clinical prognostic feature regarding survival in MSA. Patients with concomitant motor and autonomic dysfunction within three years of symptom onset had a shorter survival duration, in addition to becoming wheelchair dependent and bed-ridden at an earlier stage than those who developed these symptoms after three years from symptom onset. Their study also showed that when patients with early autonomic dysfunction develop frequent falling, or wheelchair dependence, or severe dysphagia, or require residential care, there is a shorter interval from this point to death.

Treatment

There is no discovered cure for MSA, so treatment involves controlling the symptoms.

Ongoing care from a neurologist specializing in "movement disorders" is recommended as the complex symptoms of MSA are often not familiar to less-specialized health care professionals.

One particularly serious problem, the drop in blood pressure upon standing up (with risk of fainting and thus injury from falling) often responds to fludrocortisone, a synthetic mineralocorticoid. Another common drug treatment is midodrine (an alpha-agonist). Non-drug treatments include "head-up tilt" (elevating the head of the whole bed by about 10 degrees), salt tablets or increasing salt in the diet, generous intake of fluids, and pressure (elastic) stockings. Avoidance of triggers of low blood pressure (such as hot weather, alcohol, dehydration) are crucial.

Hospice/homecare services can be very useful as disability progresses.

Levodopa (L-Dopa), a drug used in the treatment of Parkinson's disease, fails to improve the parkinsonian symptoms of most MSA patients. A recent trial reported that only 1.5% of MSA patients experienced a less than 50% improvement when taking levodopa, and even this was a transient effect lasting less than one year. Poor response to L-Dopa has been suggested as a possible element in the differential diagnosis of MSA from Parkinson's disease.

A November, 2008 study conducted in Europe failed to find an effect for the drug riluzole in treating MSA or PSP.

A July, 2012, study suggested that mesenchymal stem cell therapy could delay the progression of neurological deficits in patients with MSA-cerebellar type, suggesting the potential of mesenchymal stem cell therapy as a treatment candidate of MSA.

Rehabilitation

Management by rehabilitation professionals (physiatrists, physiotherapists, occupational therapists, speech therapists, and others) for problems with walking/movement, daily tasks, and speech problems is essential.

Physiotherapy can help to maintain the patient's mobility and will help to prevent contractures. Instructing patients in gait training will help to improve their mobility and decrease their risk of falls. A physiotherapist may also prescribe mobility aids such as a cane or a walker to increase the patient's safety. Other ways a physiotherapist can help to improve the patient's safety are to teach them to move and transfer from sitting to standing slowly to decrease risk of falls and limit the effect of postural hypotension. Instruction in ankle pumping helps to return blood in the legs to the systemic circulation. To further control the postural hypotension, raising the head of the bed by 8 in (20.3 cm) while sleeping may be indicated as well as the use of elastic compression garments.

Speech and language therapists may assist in assessing, treating and supporting speech (dysarthria) and swallowing difficulties (dysphagia). Early intervention of swallowing difficulties is particularly useful to allow for discussion around tube feeding further in the disease progression.{doubtful - citation needed} At some point in the progression of the disease, fluid and food modification may be suggested. Speech changes mean that alternative communication may be needed, for example communication aids or word charts.

Social workers and occupational therapists can also help with coping with disability through the provision of equipment and home adaptations, services for caregivers and access to healthcare services, both for the person with MSA as well as family caregivers.