Multiple System Atrophy Clinical Presentation

Updated: Nov 10, 2017
  • Author: André Diedrich, MD, PhD; Chief Editor: Selim R Benbadis, MD  more...
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Presentation

History and Physical Examination

Most patients with multiple system atrophy (MSA) develop the disease when they are older than 40 years (average 52-55y), and they experience fast progression. Usually autonomic and/or urinary dysfunction develops first. Patients with MSA may have parkinsonian symptoms with poor or nonsustained response to levodopa therapy. Only 30% of MSA-P patients have an initial transient improvement. About 90% of patients are nonresponsive to long-term levodopa therapy.

Typically, 60% of patients experience objective decline in motor function within 1 year. Motor impairment can be caused by cerebellar dysfunction. Corticospinal tract dysfunction also can occur but is not often a major symptomatic feature of MSA. Table 2a provides an overview of the clinical domains and their main features. More details are described in subsequent sections. [21]

Autonomic and/or urinary dysfunction

Autonomic symptoms are the initial feature in 41-74% of patients with MSA; these symptoms ultimately develop in 97% of patients. Genitourinary dysfunction is the most frequent initial complaint in women, and erectile dysfunction is the most frequent initial complaint in men.

Severe orthostatic hypotension

Severe orthostatic hypotension is defined as a reduction in systolic blood pressure (BP) of at least 30mm Hg or in diastolic BP of at least 15mm Hg, within 3 minutes of standing from a previous 3-minute interval in the recumbent position. This form of hypotension is common in MSA, being present in at least 68% of patients. Most patients do not respond with an adequate heart rate increase. The definition of severe orthostatic BP fall as a diagnostic criterion for MSA is stricter than the definition of orthostatic hypotension as a physical finding as defined by the American Autonomic Society. [22]

Symptoms associated with orthostatic hypotension include the following:

  • Light-headedness

  • Dizziness

  • Dimming of vision

  • Head, neck, or shoulder pain

  • Altered mentation

  • Weakness - Especially of the legs

  • Fatigue

  • Yawning

  • Slurred speech

  • Syncope

Some patients have fewer orthostatic symptoms. In 51% of patients with MSA, syncope is reported at least once. In 18% of patients with severe hypotension, more than 1 syncopal episode is documented. Because of dysautonomia-mediated baroreflex impairment and consequent debuffering, patients respond in an exaggerated fashion to drugs that raise or lower their BP.

Orthostatic hypotension must be distinguished from postural tachycardia syndrome, which is defined as an increase in heart rate of greater than 30 beats per minute (bpm) and maintained BP (absence of orthostatic hypotension).

Postprandial hypotension

Patients are also susceptible to postprandial hypotension. Altered venous capacitance and baroreflex dysfunction have been reported as a cause. [23]

Supine hypertension

Approximately 60% of patients with MSA have orthostatic hypotension and supine hypertension. The supine hypertension is sometimes severe (>190/110mm Hg) and complicates the treatment of orthostatic hypotension.

Parkinsonism

Parkinsonism can be the initial feature in 46% of patients with MSA with predominant parkinsonism (MSA-P); it ultimately develops in 91% of these MSA-P patients. Although akinesia and rigidity predominate, tremor is present at rest in 29% of patients; however, a classic pill-rolling parkinsonian rest tremor is recorded in only 8-9%. Patients with MSA-P have a poor response to levodopa.

About 28-29% of patients have a good or even excellent levodopa response early in their disease. However, only 13% maintain this response. Patients with early onset (at < 49 y) MSA-P tend to have a good levodopa response.

Patients sometimes complain of stiffness, clumsiness, or a change in their handwriting at the onset of the disease.

Cerebellar dysfunction

Cerebellar symptoms or signs are the only initial feature in 5% of MSA patients. MSA with cerebellar features (MSA-C) most commonly causes gait and limb ataxia; tremor, pyramidal signs, and myoclonus are less common findings.

Additional symptoms

Other symptoms of MSA are based on mixed dysfunction. When the disorder results in nonautonomic features, imbalance caused by cerebellar or extrapyramidal abnormalities is the most common feature.

If the cerebellar, extrapyramidal, and pyramidal systems are involved, the movement disorder is usually the most profound disability.

Vocal cord paralysis may lead to hoarseness and stridor. A neurogenic and obstructive mixed form of sleep apnea can occur.