title: The Diagnosis and Natural History of Multiple System Atrophy, Cerebellar Type.
abstract: The objective of this study was to identify key features differentiating multiple system atrophy cerebellar type (MSA-C) from idiopathic late-onset cerebellar ataxia (ILOCA). We reviewed records of patients seen in the Massachusetts General Hospital Ataxia Unit between 1992 and 2013 with consensus criteria diagnoses of MSA-C or ILOCA. Twelve patients had definite MSA-C, 53 had possible/probable MSA-C, and 12 had ILOCA. Autonomic features, specifically urinary urgency, frequency, and incontinence with erectile dysfunction in males, differentiated MSA-C from ILOCA throughout the disease course (p = 0.005). Orthostatic hypotension developed later and differentiated MSA-C from ILOCA (p < 0.01). REM sleep behavior disorder (RBD) occurred early in possible/probable MSA-C (p < 0.01). Late MSA-C included pathologic laughing and crying (PLC, p < 0.01), bradykinesia (p = 0.01), and corticospinal findings (p = 0.01). MRI distinguished MSA-C from ILOCA by atrophy of the brainstem (p < 0.01) and middle cerebellar peduncles (MCP, p = 0.02). MSA-C progressed faster than ILOCA: by 6 years, MSA-C walker dependency was 100 % and ILOCA 33 %. MSA-C survival was 8.4 ± 2.5 years. Mean length of ILOCA illness to date is 15.9 ± 6.4 years. A sporadic onset, insidiously developing cerebellar syndrome in midlife, with autonomic features of otherwise unexplained bladder dysfunction with or without erectile dysfunction in males, and atrophy of the cerebellum, brainstem, and MCP points strongly to MSA-C. RBD and postural hypotension confirm the diagnosis. Extrapyramidal findings, corticospinal tract signs, and PLC are helpful but not necessary for diagnosis. Clarity in early MSA-C diagnosis can prevent unnecessary investigations and facilitate therapeutic trials.
authors.affiliation: Ataxia Unit, Cognitive Behavioral Neurology Unit, Laboratory for Neuroanatomy and Cerebellar Neurobiology, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Lin
authors.affiliation: Ataxia Unit, Cognitive Behavioral Neurology Unit, Laboratory for Neuroanatomy and Cerebellar Neurobiology, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Hermann
authors.affiliation: Ataxia Unit, Cognitive Behavioral Neurology Unit, Laboratory for Neuroanatomy and Cerebellar Neurobiology, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA. jschmahmann@mgh.harvard.edu.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Schmahmann
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D003937:Diagnosis, Differential; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000175:diagnosis* / Q000503:physiopathology*; D009460:Neurologic Examination; D011446:Prospective Studies; D012189:Retrospective Studies; D013132:Spinocerebellar Degenerations / Q000175:diagnosis / Q000503:physiopathology; D055815:Young Adult
keywords: Ataxia; Atrophy; Autonomic neuropathy; Cerebellum; Erectile dysfunction; Idiopathic late-onset cerebellar ataxia; Middle cerebellar peduncle; Multiple system atrophy; Parkinsonism; Pathologic laughing and crying; Pons; REM sleep behavior disorder; Sporadic adult-onset ataxia; Urinary incontinence