What are the histologic features of multiple system atrophy (MSA)?

Updated: Oct 17, 2018
  • Author: André Diedrich, MD, PhD; Chief Editor: Selim R Benbadis, MD  more...
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Neuropathologic changes in MSA consist of the development of a high density of GCIs in association with degenerative changes in some or all of the following structures (Table 5 provides an overview of the clinicopathologic correlation):

  • Putamen

  • Caudate nucleus

  • Globus pallidus

  • Thalamus

  • Subthalamic nucleus

  • Substantia nigra

  • Locus ceruleus

  • Dorsal vagal nucleus

  • Vestibular nuclei

  • Pontine nuclei

  • Inferior olives

  • Pontine nuclei

  • Cerebellar Purkinje cells

  • Autonomic nuclei of the brainstem

  • Intermediolateral cell columns

  • Anterior horn cells

  • Onuf nuclei in the spinal cord and pyramidal tracts

GCIs, which can be stained using the Gallyas silver technique, range from sickle shaped to flame shaped to ovoid, on occasion, superficially resembling neurofibrillary tangles. GCIs are loosely aggregated filaments with cross-sectional diameters of 20-30 nm. These filaments often entrap cytoplasmic organelles (eg, mitochondria, secretory vesicles), have no limiting membrane, and have tubular profiles and electrodense granules along much of their lengths. GCIs are ubiquitin-positive, tau-positive, and alpha-synuclein ̶ positive oligodendroglial inclusions. They are different from Lewy bodies and neurofibrillary structures in Alzheimer disease. (See Table 8, below.)

Table 8. Differences Between GCIs in MSA and Other Pathologic Inclusions and Structures (Open Table in a new window)



Lewy Bodies in Parkinson Disease

Neurofibrillary Pathology in Alzheimer Disease

Glial Lesions in Corticobasal and Progressive Supranuclear Palsy


Sickle shaped to flame shaped to ovoid, various neurofibrillary tangles

Target-shaped inclusions


Tufted astrocytes, coiled bodies


No limiting membrane; tubular profiles and electrodense granules





Loosely aggregated filaments

No data

No data

Astrocytic plaques


Ubiquitin positive, alpha-B-crystallin (synuclein) positive, alpha- and beta-tubulin positive, tau-protein positive

Hyaline eosinophilic cytoplasmic neuronal inclusions, ubiquitin

No data

Absence of phosphorylated tau


In oligodendroglial cells and neurons

In neuronal cells and oligodendroglial cells

No data

No data

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