Table 1 Diagnostic Criteria for definite, probable, and possible multiple system atrophy (MSA) [1]

Definite MSA

 • Neuropathological demonstration of α-synclein-positive glial cytoplasmic inclusions with neurodegenerative changes in striatonigral or olivopontocerebellar structures

 • A sporadic and progressive adult onset (>30 y) disease characterized by the symptoms below

Probable MSA

 • Autonomic dysfunction including urinary dysfunction (inability to control the release of urine from the bladder, with erectile dysfunction in males) or orthostatic hypotension (decrease of blood pressure within 3 min by at least 30 mm Hg systolic or 15 mm Hg diastolic

 • Plus parkinsonism (bradykinesia with rigidity, tremor, or postural instability), which responds poorly to L-dopa, or cerebellar symptoms (gait ataxia with dysathria, limb ataxia, or cerebellar oculomotor dysfunction)

Possible MSA

 • Parkinsonism (bradykinesia with rigidity, tremor, or postural instability) or same cerebellar symptoms as Probable MSA

 • Plus at least one feature suggesting autonomic dysfunction (otherwise unexplained urinary urgency, frequency or incomplete bladder emptying, erectile dysfunction in males, or orthostatic hypotension not meeting criteria of Probable MSA) and at least one of the additional features below

Additional features of Possible MSA

 MSA-P or MSA-C

  • Babinski sign with hyperreflexia

  • Stridor

 Possible MSA-P

  • Rapidly progressive parkinsonism

  • Poor response to L-dopa

  • Postural instability within 3 y of motor onset

  • Gait ataxia, cerebellar dysarthria, or cerebellar oculomotor dysfunction

  • Dysphasia within 5 y of motor onset

  • Atrophy in MRI of putamen, middle cerebellar penducle, pons, or cerebellum

  • Hypometabolism in putamen, brainstem, or cerebellum on FDG-PET

 Possible MSA-C

  • Parkinsonism (bradykinesia and rigidity)

  • Atrophy in MRI of putamen, middle cerebellar penducle, or pons

  • Hypometabolism in putamen on FDG-PET

  • Presynaptic nigrostriatal dopaminergic denervation in SPECT or PET imaging

Features supporting (red flag) and not supporting a diagnosis of MSA

 Supporting features

  • Orofacial dystonia

  • Disproportionate antecollis

  • Severe dysphoria

  • Contractures of hands or feet

  • Inspiration signs

  • Camptocormia (severe anterior flexion of the spine) and/or Pisa syndrome (severe lateral flexion of the spine)

  • Severe dysarthria

  • New or increased snoring

  • Cold hands and feet

  • Pathologic laughter or crying

  • Jerky, myoclonic postural/action tremor

 Nonsupporting features

  • Classic pill-rolling rest tremor

  • Clinically significant neuropathy

  • Hallucination not induced by drugs

  • Onset after age 75 y

  • Family history of ataxia or parkinsonism

  • Dementia (for DSM-IV)

  • White matter lesions supporting multiple sclerosis