Diagnostic Criteria for Multiple-System Atrophy (MSA)

Multiple system atrophy (MSA) is a sporadic and fatal alpha-synuclein-linked oligodendrogliopathy manifesting with progressive autonomic failure, poorly levodopa-responsive parkinsonism, and cerebellar ataxia, in any combination.

Diagnostic Criteria for Multiple-System Atrophy (MSA)

Definite MSA

Neuropathological findings during postmortem examination must include the following:

  • Widespread and abundant cerebral alpha-synuclein–positive GCIs
  • Neurodegenerative changes in striatonigral or olivopontocerebellar region

Probable MSA

Sporadic, progressive disease in adults (onset after 30 yr of age) characterized by autonomic failure, including urinary incontinence (with erectile dysfunction in men), or an orthostatic decrease in blood pressure by at least 30 mm Hg systolic or 15 mm Hg diastolic within 3 min of standing, plus one of the following:

  • Parkinsonism (slowness of movements, rigidity, and tendency to fall) with poor response to levodopa (parkinsonian subtype [MSA-P])
  • A cerebellar syndrome (wide-based gait, uncoordinated limb movements, action tremor, and nystagmus) (cerebellar subtype [MSA-C])

Possible MSA

A sporadic, progressive, adult-onset disease characterized by the following:

* Parkinsonism (slowness of movements, rigidity, and tendency to fall) or a cerebellar syndrome (wide-based gait, uncoordinated limb movements, action tremor, and nystagmus)
* At least one feature suggesting autonomic dysfunction (otherwise unexplained urinary urgency or frequency, incomplete bladder emptying, erectile dysfunction in men, or a substantial orthostatic blood-pressure decline that does not meet the level required for probable MSA)
* At least one of the following additional features:

  • Possible MSA-P or MSA-C: Babinski sign with hyperreflexia, stridor
  • Possible MSA-P: rapidly progressive parkinsonism; poor response to levodopa; recurrent falls within 3 yr after the onset of motor symptoms; cerebellar features (wide-based gait; cerebellar dysarthria; uncoordinated limb movements; or spontaneous, gaze-evoked, or positional downbeat nystagmus); recurrent choking within 5 yr after the onset of motor symptoms; atrophy on MRI of the putamen, middle cerebellar peduncle, pons, or cerebellum; hypometabolism on FDG-PET in the putamen, brain stem, or cerebellum
  • Possible MSA-C: parkinsonism; atrophy on MRI of the putamen, middle cerebellar peduncle, or pons; hypometabolism on FDGPET in the putamen; presynaptic nigrostriatal dopaminergic denervation on SPECT or PET

Features supporting the diagnosis of MSA (red flags) and features not supporting the diagnosis

  • Supporting: head–neck dystonia; disproportionate antecollis; bent spine (forward, lateral, or both); contractures of the hands or feet; inspiratory sighs; severe dysphonia; severe dysarthria; new or increased snoring; cold hands and feet; emotional incontinence (pathologic laughter or crying); jerky, irregular, or postural or action tremor
  • Not supporting: classic “pill-rolling” rest tremor, clinically significant neuropathy, hallucinations not induced by drugs, onset after 75 yr of age, family history of ataxia or parkinsonism, dementia (in accordance with DSM-IV criteria), white-matter lesions suggesting multiple sclerosis

*FDG-PET [18F]-fluorodeoxyglucose–positron-emission tomography; GCI glial cytoplasmic inclusion; and SPECT single-photon-emission computed tomography.

 

 

References:

  1. Fanciulli A, Wenning GK. Multiple-system atrophy. N Engl J Med. 2015 Jan 15;372(3):249-63 [Medline]
  2. Wenning GK, Krismer F. Multiple system atrophy. Handb Clin Neurol. 2013;117:229-41. [Medline]
  3. Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, Wood NW, Colosimo C, Dürr A, Fowler CJ, Kaufmann H, Klockgether T, Lees A, Poewe W, Quinn N, Revesz T, Robertson D, Sandroni P, Seppi K, Vidailhet M. Second consensus statement on the diagnosis of multiple system atrophy. Neurology. 2008 Aug 26;71(9):670-6. [Medline]

Created Apr 14, 2015.

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