Multiple system atrophy of the cerebellar type: Clinical state of the art

Abstract

Multiple system atrophy (MSA) is a late-onset, sporadic neurodegenerative disorder clinically characterized by autonomic failure and either poorly levodopa-responsive parkinsonism or cerebellar ataxia. It is neuropathologically defined by widespread and abundant central nervous system α-synuclein-positive glial cytoplasmic inclusions and striatonigral and/or olivopontocerebellar neurodegeneration. There are two clinical subtypes of MSA distinguished by the predominant motor features: the parkinsonian variant (MSA-P) and the cerebellar variant (MSA-C). Despite recent progress in understanding the pathobiology of MSA, investigations into the symptomatology and natural history of the cerebellar variant of the disease have been limited. MSA-C presents a unique challenge to both clinicians and researchers alike. A key question is how to distinguish early in the disease course between MSA-C and other causes of adult-onset cerebellar ataxia. This is a particularly difficult question, because the clinical framework for conceptualizing and studying sporadic adult-onset ataxias continues to undergo flux. To date, several investigations have attempted to identify clinical features, imaging, and other biomarkers that may be predictive of MSA-C. This review presents a clinically oriented overview of our current understanding of MSA-C with a focus on evidence for distinguishing MSA-C from other sporadic, adult-onset ataxias.

Canine Hereditary Ataxia

“…47 MSA-C but not MSA-P is commonly placed under the Hereditary Ataxia umbrella. The authors have provided a description of these diseases in 2 breeds of dogs because their initial presentation is typically one of cerebellar ataxia and there are obvious cerebellar lesions.…”

The Diagnosis and Natural History of Multiple System Atrophy, Cerebellar Type

“…The critical unanswered question for the clinician evaluating a patient with ataxia, however, is how to differentiate MSA-C from the many other causes of adult-onset cerebellar ataxias, 28 the differential diagnosis of which includes acquired (including toxins, tumors, and infections), genetic (spinocerebellar ataxias) and sporadic etiologies. 29,30 A complete history, examination, and laboratory investigations including magnetic resonance imaging (MRI), can differentiate many disorders from MSA-C, but for the adult patient presenting with an insidious onset, pure or predominantly cerebellar ataxia with no family history or apparent inciting event, distinguishing idiopathic late-onset cerebellar ataxia (ILOCA) from MSA-C early in the disease course remains a major diagnostic challenge.…”

Idiopathic very late-onset cerebellar ataxia: A Brazilian case series

“…Currently, alternative terms have been used to describe to this group of patients, such as sporadic adult onset ataxia of unknown etiology (SAOA), or idiopathic late-onset pure cerebellar ataxia (ILOPCA), among others 1,2,6,7,8 . MSA-C represents the main differential diagnosis of ILOCA 8,9 . This group of non-hereditary degenerative ataxias needs to be differentiated from hereditary ataxias (with late-onset and no familial history), and acquired ataxias, which are due to exogenous or endogenous non-genetic causes.…”