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multiple system atrophy (MSA)

Variants of multiple system atrophy include: 1) striatonigral degeneration 2) Shy-Drager syndrome 3) olivopontocerebellar atrophy (OPCAs) 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: 1) argyrophilic glial & neuronal cytoplasmic inclusions [4] a) appearance of tangles of microtubules b) contain alpha synuclein, ubiquitin & tau mostly 2) degenerative changes & cell loss in many CNS structures: a) striatum - most severe dorsal posterior 2/3 of putamen - also external globus pallidus b) substantia nigra - zona compacta, primarily lateral third c) locus ceruleus d) cerebellum - Purkinje cells, with granule cells relatively spared e) middle cerebellar peduncle f) inferior olives g) basal pontine nuclei h) intermediolateral horn cells i) dorsal motor nucleus of vagus nerve j) ventrolateral reticular formation - catecholaminergic cells k) arcuate nucleus l) Onuf's nucleus Clinical manifestations: 1) parkinsonism (can be asymmetric) a) bradykinesia b) rigidity c) postural instability d) hypokinetic speech, hypophonia e) +/- tremor (classical pill-rolling rest tremor uncommon) f) irregular postural tremor & action tremor with superimposed jerks in 50% [9] 2) cerebellar dysfunction a) cerebellar ataxia - gait ataxia, limb ataxia b) postural instability, early loss of postural reflexes c) early & recurrent falls d) dysmetria, abnormal finger to nose e) ataxic dysarthria f) disorders of extraocular movements 3) autonomic insufficiency a) orthostatic hypotension, often with inadequate heart rate response to standing b) erectile dysfunction c) constipation d) decreased sweating 4) urinary symptoms a) urinary urgency, urinary frequency, urinary incontinence b) nocturia 5) pyramidal tract signs 6) stimulus-sensitive myoclonus of hands & face 7) extreme forward neck flexion 8) mottled, cold hands 9) inspiratory stridor, nocturnal stridor [8] 10) REM sleep disorder 11) prominent dysarthria - vocal cord paralysis 12) rapid progression of disease 13) 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: 1) PET studies similiar for different disorders -> fluorodopa, opioid binding, glucose 2) MRI a) striatal abnormalities: 1] atrophy of the putamen 2] slit-like signal change at posterolateral margin of the putamen 3] hypointensity of putamen relative to globus pallidus b) cerebellar atrophy c) pontine atrophy d) signal changes in pons & middle cerebellar peduncles 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) a) generally no response due to loss of striatal neurons containing dopamine receptors b) 20% of patients with good initial response c) 13% with sustained response d) patients wheel-chair bound despite response to Sinemet

Interactions

disease interactions

Specific

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)

General

parkinson plus syndrome synucleinopathy (includes alpha-synucleinopathy)

Figures/Diagrams

Figures/diagrams/slides/tables related to multiple system atrophy

Properties

PATHOLOGY: glial cytoplasmic inclusion neuronal cytoplasmic inclusion

References

  1. Diseases of the Nervous System. Clinical Neurobiology. Asbury, McKhann, McDonald eds. Saunders 1992 2nd ed.
  2. Lang AE & Lazano AM Parkinson's disease. First of two parts. NEJM 339(15):1044-53 1998 PMID: 9761807
  3. Goedert M Alpha-synuclein and neurodegenerative diseases. Nature Reviews Neuroscience 2:492-501, 2001 PMID: 11433374
  4. Gilman S et al Consensus statement on the diagnosis of multiple system atrophy. J Neurol Sci 163:94-8, 1999 PMID: 10223419
  5. Bronstein J, In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 29-Oct 2, 2004
  6. 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: 21236720
  7. Wenning GK, Colosimo C. Diagnostic criteria for multiple system atrophy and progressive supranuclear palsy. Rev Neurol (Paris). 2010 Oct;166(10):829-33
  8. Medical Knowledge Self Assessment Program (MKSAP) 17, American College of Physicians, Philadelphia 2015
  9. Geriatric Review Syllabus, 10th edition (GRS10) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2019
  10. Palma JA, Norcliffe-Kaufmann L, Kaufmann H. Diagnosis of multiple system atrophy. Auton Neurosci. 2018 May;211:15-25. PMID: 29111419 PMCID: PMC5869112 Free PMC article. Review.