Multiple System Atrophy

Diseases,

Synonyms:

formerly Shy-Drager syndrome/Striatonigral degeneration, formerly included under olivopontocerebelar atrophy OPCA

Diagnosis:

This is based on clinical features supported by consistent investigations

Clinical features:

Parkinsonism
+other features:

  • Ataxia
  • Early falls forward
  • Autonomic failure:
    • Othostatic hypotension, syncope
    • Impotence, urinary retention, constipation
    • Axial rigidity
  • Laryngeal stridor
  • Hypometric saccadic eye movements
  • Coat hanger sign: a sensation of being suspended from a coat hanger when standing upright.

Subtypes:

2 subtypes: MSA-P (parkinsonian predominant), MSA-C (cerebellar predominant).
Debated (old terminology):

  • Shy Drager syndrome SDS: +dysautonomia
  • Sporadic Olivopontocerebellar atrophy OPCA: +
  • Striatonigral degeneration SND

Pathology:

Gross:

  • Both; pallor of substantia nigra. MSA-P discolouration & atrophy of the Putamen, atrophy of the caudate nucleus. MSA-C atrophy of the cerebellum, middle cerebellar peduncle and pons.

Microscopically:

  • Both; neuronal loss and astrocytic gliosis in pons, accessory and inferior olivary nuclei, locus ceruleus, medulla, arcuate nucleus and in hypothalamus and intermediolateral cell column.
  • MSA-P neuronal loss and astrocytosis in putamen and caudate nucleus;
  • MSA-C; Purkinje cell loss in cerebellar vermis>hemispheres.

Immunohistochemistry:

  • Alpha-synuclein and ubiquitin positive oligodendroglial Glial Cytoplasmic Inclusions GCI in pyramidal, extrapyramidal, limbic, corticocerebellar and supraspinal autonomic systems.
  • Variable tau immunoreactivity.
  • Sliver stain: also stains alpha-synuclein.
  • Epicardial space nerve fibres: Tyrosine hydroxylase staining is normal (no cardiac denervation, sympathetic)

Findings on investigations:

  • Intact Cardiac innervation by:
  • Cardiac SPECT 123I –labeled MIBG, reduced uptake
  • PET scan

MRI:

  • DWI MRI, ADC: increased regional ADC, rADC in middle cerebellar peduncle. This is normal in Parkinson disease and in progressive supranuclear palsy PSP.
  • Autonomic nervous system testing: panautonomic failure.

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