Multiple system atrophy (MSA) is a sporadic neurodegenerative disease (one of the synucleinopathies) characterized by varying degrees of cerebellar ataxia, autonomic dysfunction, parkinsonism and corticospinal dysfunction.
Multiple systemic atrophy is a sporadic disease, with a prevalence of 4 per 100,000 2. Typically symptoms begin between 40 and 60 years of age 2.
Clinical presentation is variable, but typically presents in one of three patterns (initially described as separate entities) 1,2:
- Shy-Drager syndrome is used when autonomic symptoms predominate
- striatonigral degeneration shows predominant parkinsonian features
- olivopontocerebellar atrophy demonstrates primarily cerebellar dysfunction
In a 2007 consensus paper 6 MSA has been divided clinically into two forms according to the dominant non-autonomic symptoms:
- MSA-C: predominance of cerebellar symptoms (olivopontocerebellar atrophy)
- MSA-P: predominance of parkinsonian signs and symptoms (striatonigral degeneration)
Some older texts refer to MSA-A to denote Shy-Drager syndrome. In the latest consensus however autonomic symptoms are considered part of both MSA-C and MSA-P and thus the term MSA-A is no longer used.
Like other synucleinopathies, multiple systemic atrophy results from abnormalities of alpha-synuclein metabolism, resulting in intracellular deposition. Unlike Parkinson disease and Lewy body dementia (two other synucleinopathies) these intracellular deposits are found not only in neurons but also in oligodendroglia 2.
MRI is the modality of choice for imaging patients with suspected multiple system atrophy (MSA).
- T2: hyperintensities typically present in the pontocerebellar tracts
putaminal findings in MSA-P 5:
- reduced volume
- reduced GRE and T2 signal relative to globus pallidus
- reduced GRE and T2 signal relative to the red nucleus
- abnormally high T2 linear rim surrounding the putamen (putaminal rim sign), seen at 1.5 T (this is normal at 3 T) 7 (see case 3)
- disproportionate atrophy of the cerebellum and brainstem (especially olivary nuclei and middle cerebellar peduncle)
- ADC values: higher in the pons, cerebellum, and putamen than in Parkinson disease or controls
- fractional anisotropy (FA): lower in the pons, cerebellum, and putamen than in Parkinson disease or controls
On SPECT/CT with I-123 ioflupane, there is loss of the normal comma- or crescent-shaped tracer uptake in the striatum. Instead, a period- or oval-shaped uptake is seen within the caudate nucleus head without tracer uptake in the putamen. Quantitative assessment reveals reduced uptake in the putamen compared to norms.
Treatment and prognosis
Unfortunately, no effective treatment is currently available. The disease progresses relentlessly culminating in death usually within 10 years of diagnosis 2.
- 1. Grossman RI, Yousem DM. Neuroradiology, the requisites. Mosby Inc. (2003) ISBN:032300508X. Read it at Google Books - Find it at Amazon
- 2. Kornienko VN, Pronin IN. Diagnostic Neuroradiology. Springer Verlag. (2008) ISBN:3540756523. Read it at Google Books - Find it at Amazon
- 3. Matsusue E, Fujii S, Kanasaki Y et-al. Cerebellar lesions in multiple system atrophy: postmortem MR imaging-pathologic correlations. AJNR Am J Neuroradiol. 2009;30 (9): 1725-30. doi:10.3174/ajnr.A1662 - Pubmed citation
- 4. Ozawa T, Paviour D, Quinn NP et-al. The spectrum of pathological involvement of the striatonigral and olivopontocerebellar systems in multiple system atrophy: clinicopathological correlations. Brain. 2004;127 (Pt): 2657-71. doi:10.1093/brain/awh303 - Pubmed citation
- 5. Lee JY, Yun JY, Shin CW et-al. Putaminal abnormality on 3-T magnetic resonance imaging in early parkinsonism-predominant multiple system atrophy. J. Neurol. 2010;257 (12): 2065-70. doi:10.1007/s00415-010-5661-x - Pubmed citation
- 6. Gilman S, Wenning GK, Low PA et-al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology. 2008;71 (9): 670-6. doi:10.1212/01.wnl.0000324625.00404.15 - Free text at pubmed - Pubmed citation
- 7. Lee WH, Lee CC, Shyu WC et-al. Hyperintense putaminal rim sign is not a hallmark of multiple system atrophy at 3T. AJNR Am J Neuroradiol. 2005;26 (9): 2238-42. AJNR Am J Neuroradiol (full text) - Pubmed citation
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neurodegenerative MRI brain (an approach)
- measurements and ratios
- midbrain to pons area ratio (for PSP)
- Magnetic Resonance Parkinsonism Index (MRPI) (for PSP)
- frontal horn width to intercaudate distance ratio (FH/CC) (for Huntington disease)
- intercaudate distance to inner table width ratio (CC/IT) (for Huntington disease)
- scoring systems
- measurements and ratios
- typical/classical Alzheimer disease
- variant (e.g. posterior cortical atrophy)
- chronic traumatic encephalopathy (CTE)
- corticobasal degeneration
- frontotemporal lobar degeneration (FTLD) (not all are tau)
- Pick disease
- progressive supranuclear palsy (PSP)
- Alzheimer disease
- cerebral amyloid angiopathy (CAA)
- transthyretine-associated cerebral amyloidosis
- neuronal intranuclear hyaline inclusion disease (NIHID)
- TDP-43 proteinopathies
- spinocerebellar ataxias
- Huntington disease
- hereditary spastic paraplegia
- clinically unclassifiable parkinsonism (CUP)
- Unverricht-Lundborg disease
- prion diseases (not always included as neurodegenerative)