How is multiple system atrophy (MSA) differentiated from pure autonomic failure (PAF)?

Updated: Oct 17, 2018
  • Author: André Diedrich, MD, PhD; Chief Editor: Selim R Benbadis, MD  more...
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Answer

MSA and PAF

Patients with MSA who present with only autonomic and urinary dysfunction can be incorrectly identified as having pure autonomic failure (PAF).

Bradbury and Eggleston first described PAF as idiopathic hypotension, [28] but current criteria imply failure of the autonomic nervous system in the absence of extrapyramidal, pyramidal, or cerebellar abnormalities. MSA is distinct from PAF.

The sympathetic and parasympathetic systems are centrally impaired in MSA, whereas the involvement is peripheral in PAF. The progression of MSA is faster than that of PAF, and the prognosis is poor.

Lewy bodies are common in PAF at many sites, even occasionally in the heart, but they are not present in MSA. (Exception: In 1999, Pakiam et al reported 1 case in which a patient with diffuse Lewy-body disease presented with parkinsonism and prominent autonomic dysfunction, fulfilling proposed criteria for the striatonigral form of MSA. [27] ) Instead of Lewy bodies, patients with MSA have oligodendroglial cytoplasmic inclusions. Low plasma norepinephrine levels also usually indicate PAF.

Table 7, below, summarizes the distinctive features of MSA and PAF. Early (eg, years 1-2) in the disease process, the distinction may be difficult, but distinguishing findings are usually evident during follow-up care.

Table 7. Differential Diagnosis of MSA and PAF (Open Table in a new window)

Characteristic

MSA

Pure Autonomic Failure

CNS involvement

Multiple involvement

Unaffected

Site of lesion

Mainly preganglionic, central; degeneration of intermediolateral cell columns; ganglionic neurons relatively intact

Mainly postganglionic; loss of ganglionic neurons

Progression

Fast; median survival 6.5-9.5 years

Slow; some patients survive >10-30 years

Prognosis

Poor

Good

Extrapyramidal involvement

Common

Not present

Cerebellar involvement

Common

Not present

Gastrointestinal symptoms

Uncommon

Absent, except constipation

Plasma supine norepinephrine level

Normal

Reduced

Antidiuretic hormone (ADH) response to tilt

Impaired because of catecholaminergic denervation of hypothalamus (but normal ADH response to osmotic stimuli)

Maintained

Adrenocorticotropic hormone and beta-endorphin response to hypoglycemia

Impaired because of central cholinergic dysfunction or dysfunction of adrenergic input to paraventricular nucleus

Normal

Growth hormone release with clonidine IV injection

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

Increase of growth hormone; intact function

Substance P, catecholamine, 5-HT, and acetylcholine markers in cerebrospinal fluid

Decreased levels

No data

Lewy bodies

Mostly absent

Present in autonomic neurons

BP response to oral water intake

Increased

Increased but variable

BP response to ganglionic blockade

Profound decrease

Modest decrease


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