Chapter 3 Multiple System Atrophy

Abstract

Publisher Summary This chapter discusses the concept of multiple system atrophy. Multiple system atrophy (MSA) comprises three manifestations described as olivopontocerebellar atrophy (OPCA), Shy–Drager syndrome (SDS), and striatonigral degeneration (SND). Cerebellar ataxia, Parkinsonism with short-lasting response to levodopa, and autonomic failure with incontinence and orthostatic dysfunction are clinical hallmarks of the disease, whereas dementia, pill-rolling tremor, gaze palsy, and marked neuropathy are uncommon in MSA. Magnetic resonance imaging (MRI), (123I)-metaiodobenzylguanidine (MIBG), and singlephoton emission computed tomography (SPECT) are useful tools in the differentiation of MSA to Parkinson's disease (PD) and idiopathic cerebellar ataxia. Oligodendroglial cytoplasmic inclusions (GCIs) containing ubiquitin, tau, and α-synuclein constitute the pathologic hallmark in all three clinical subtypes of MSA. Because of the abundant presentation of α-synuclein in GCIs, MSA is regarded as a synucleinopathy. The overexpression of α-synuclein in genetically modified mice in combination with 3-nitropropionic acid toxicity replicated strikingly human neuropathology. These mouse models provide new tools to disclose the basic pathophysiologic mechanisms of MSA. At present, pharmacotherapy is restricted to the symptomatic treatment of Parkinsonism, autonomic failure, sleep disturbance, and depression. Physiotherapy, speech therapy, and occupational therapy help to maintain mobility as long as possible and improve functional ability in daily living.