How is multiple system atrophy (MSA) differentiated from Parkinson disease?

Updated: Oct 17, 2018
  • Author: André Diedrich, MD, PhD; Chief Editor: Selim R Benbadis, MD  more...
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Clinical differentiation of Parkinson disease from MSA is extremely difficult. MSA is suggested by the following characteristics:

  • Disability progresses rapidly

  • Patients are poorly responsive to levodopa

  • Autonomic features such as urinary retention or incontinence or orthostatic hypotension are pronounced

  • Rigidity and bradykinesia are out of proportion to tremor

  • Speech is affected severely (dysarthrophonia, severe dysarthria)

  • Aspiration, inspiratory gasps, and stridor are present

Preliminary results of an ongoing comparison study indicate that autonomic indices are significantly more abnormal in MSA than in Parkinson disease. [24]

Wenning et al developed a predictive model based on established pathologic data from patients with MSA and Parkinson disease. [25] The model contains the following features:

  • Poor response to levodopa

  • Autonomic features

  • Speech or bulbar dysfunction

  • Absence of dementia

  • Absence of levodopa-induced confusion

  • Falls

Table 6 (below) further outlines some distinctive features of MSA and Parkinson disease.

Table 6. Differential Diagnosis of MSA and Parkinson Disease [26] (Open Table in a new window)



Parkinson Disease

Response to chronic levodopa therapy*

Poor or unsustained motor response because of loss of postsynaptic dopamine receptors

Initial improvement in 30% of patients with MSA, but 90% were unresponsive over a longer time; 50% develop levodopa-induced dyskinesia of orofacial and neck muscles

Good response

Effects on striatonigral transmission

Presynaptic and postsynaptic; dopaminergic cell bodies in substantia nigra and their terminals in striatum, as well as their striatal target cells, have reduced dopamine receptors


Symmetry of movement disorder

Possibly asymmetrical

No data

Progression of symptoms



Postural instability and falling**


Fast progression

Worsen >20% of UPDRS scale**


Less progression (< 10%)

Progress of disability

Relatively fast disability; 30% decrease of activities of daily living in 1 year; 40% of patients in a wheelchair within 5 years (wheel chair sign)

Relatively slow disability

Abnormal speech

Severely affected speech in 30% of patients with MSA

Dysarthrophonia and severe dysarthria are common

Less affected

Abnormal Respiration

Abnormal aspiration, inspiratory gasps, and stridor in 60% of patients with MSA

Stridor caused by paralysis of vocal cord occurs especially at night but is also present during day

Less common

Lewy bodies (hyaline eosinophilic cytoplasmic neuronal inclusions)

Not present***

Primarily in substantia nigra

Cytoplasmic inclusions (immunocytochemical reaction with antibodies to alpha synuclein)

Glial inclusions; argyrophilic cellular inclusions in oligodendrocytes


Thermoregulation, skin perfusion

Cold hands and decrease of warm-up after cold-pack stimulus


Caudate-putamen index of dopamine uptake (on positron emission tomography [PET] scanning)

Decreased in putamen and caudate

Decreased in putamen with smaller decrease in caudate

Growth hormone release with intravenous (IV) injection of clonidine

No release; dysfunction of hypothalamic-pituitary pathway (alpha2-adrenoceptor-hypothalamic deficit)

Increase of growth hormone, intact function

* A positive response to levodopa is defined as a significant improvement of motor features during 3 months’ application of escalating doses of levodopa with a peripheral decarboxylase inhibitor. [6]

** Postural instability as defined by item 30 of the Unified Parkinson's Disease Rating Scale (UPDRS) part III (motor examination). [6]

*** Pakiam et al reported that patients with diffuse Lewy-body disease may present with parkinsonism and prominent autonomic dysfunction, fulfilling some proposed criteria for the striatonigral form of MSA. [27]   

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