multiple system atrophy (MSA)
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Introduction
Variants of multiple system atrophy include:
Etiology
undetermined
Epidemiology
- disorder of middle age, onset usually age 50-60 years[9]
- progressing over 1-18 years, median survival 9.3 years
Pathology
- argyrophilic glial & neuronal cytoplasmic inclusions[4]
- appearance of tangles of microtubules
- contain alpha synuclein, ubiquitin & tau mostly
- degenerative changes & cell loss in many CNS structures:
- striatum - most severe dorsal posterior 2/3 of putamen
- substantia nigra - zona compacta, primarily lateral third
- locus ceruleus
- cerebellum - Purkinje cells, with granule cells relatively spared
- middle cerebellar peduncle
- inferior olives
- basal pontine nuclei
- intermediolateral horn cells
- dorsal motor nucleus of vagus nerve
- ventrolateral reticular formation
- arcuate nucleus
- Onuf's nucleus
Clinical manifestations
- parkinsonism (can be asymmetric)
- bradykinesia
- rigidity
- postural instability
- hypokinetic speech, hypophonia
- +/- tremor (classical pill-rolling rest tremor uncommon)
- irregular postural tremor & action tremor with superimposed jerks in 50%[9]
- cerebellar dysfunction
- cerebellar ataxia
- gait ataxia, limb ataxia
- postural instability, early loss of postural reflexes
- early & recurrent falls
- dysmetria, abnormal finger to nose
- ataxic dysarthria
- disorders of extraocular movements
- cerebellar ataxia
- autonomic insufficiency
- orthostatic hypotension, often with inadequate heart rate response to standing
- erectile dysfunction
- constipation
- decreased sweating
- urinary symptoms
- pyramidal tract signs
- stimulus-sensitive myoclonus of hands & face
- extreme forward neck flexion
- mottled, cold hands
- inspiratory stridor, noctural stridor[8]
- REM sleep disorder
- prominent dysarthria - vocal cord paralysis
- rapid progression of disease
- no sensory symptoms[8]
Laboratory
- higher levels of neurofilament light chain in serum in multiple system atrophy or progressive supranuclear palsy than in Parkinson's disease & healthy controls
Radiology
- PET studies similiar for different disorders
- MRI
- striatal abnormalities:
- atrophy of the putamen
- slit-like signal change at posterolateral margin of the putamen
- hypointensity of putamen relative to globus pallidus
- cerebellar atrophy
- pontine atrophy
- signal changes in pons & middle cerebellar peduncles
- striatal abnormalities:
Differential diagnosis
- Parkinson's disease: early cerebellar signs unlikely
- progressive supranuclear palsy
- supranuclear vertical ophthalmoplegia, thus extraocular eye movements & cranial nerves NOT intact
Management
- levodopa/carbidopa (Sinemet)
- generally no response due to loss of striatal neurons containing dopamine receptors
- 20% of patients with good initial response
- 13% with sustained response
- patients wheel-chair bound despite response to Sinemet
More general terms
More specific terms
- olivopontocerebellar atrophy (OPCA) or degeneration (OPCD); multiple system atrophy, cerebellar subtype
- Shy-Drager syndrome; multiple system atrophy with postural hypotension; parkinsonism with prominent dysautonomia
- striatonigral degeneration; nigrostriatal degeneration; multiple system atrophy with predominant parksinsonism (MSA-P)
References
- ↑ Diseases of the Nervous System. Clinical Neurobiology. Asbury, McKhann, McDonald eds. Saunders 1992 2nd ed.
- ↑ Lang AE & Lazano AM Parkinson's disease. First of two parts. NEJM 339(15):1044-53 1998 PMID: https://www.ncbi.nlm.nih.gov/pubmed/9761807
- ↑ Goedert M Alpha-synuclein and neurodegenerative diseases. Nature Reviews Neuroscience 2:492-501, 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11433374
- ↑ 4.0 4.1 Gilman S et al Consensus statement on the diagnosis of multiple system atrophy. J Neurol Sci 163:94-8, 1999 PMID: https://www.ncbi.nlm.nih.gov/pubmed/10223419
- ↑ Bronstein J, In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 29-Oct 2, 2004
- ↑ Messina D, Cerasa A, Condino F et al Patterns of brain atrophy in Parkinson's disease, progressive supranuclear palsy and multiple system atrophy. Parkinsonism Relat Disord. 2011 Mar;17(3):172-6 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21236720
- ↑ Wenning GK, Colosimo C. Diagnostic criteria for multiple system atrophy and progressive supranuclear palsy. Rev Neurol (Paris). 2010 Oct;166(10):829-33
- ↑ 8.0 8.1 8.2 Medical Knowledge Self Assessment Program (MKSAP) 17, American College of Physicians, Philadelphia 2015
- ↑ 9.0 9.1 9.2 Geriatric Review Syllabus, 10th edition (GRS10) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2019
- ↑ Palma JA, Norcliffe-Kaufmann L, Kaufmann H. Diagnosis of multiple system atrophy. Auton Neurosci. 2018 May;211:15-25. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29111419 PMCID: PMC5869112 Free PMC article. Review.