Multiple System Atrophy

Abstract

Multiple system atrophy (MSA) is a rare adult-onset synucleinopathy associated with dysautonomia and the variable presence of poorly levodopa-responsive parkinsonism and/or cerebellar ataxia. Other clinical symptoms that can be associated with MSA include hyperreflexia, stridor, sleep apnea, and rapid eye movement sleep behavior disorder (RBD). Mean survival from time of diagnosis ranges between 6 to 10 years, and definitive diagnosis is made on autopsy with demonstration of oligodendroglial cytoplasmic inclusions consisting of fibrillar α-synuclein. Magnetic resonance imaging (MRI) may be positive for cruciform T2 hyperintensity within the pons (the "hot cross bun sign"), volume loss in the pons and cerebellum, and T2 signal loss in the dorsolateral putamen with hyperintense rim on fluid attenuated inversion recovery (FLAIR) sequencing. Although most cases are sporadic, genetic polymorphisms have been identified both in familial and sporadic cases of MSA, and influence observed phenotypes. Treatment is symptomatic, with both pharmacological and nonpharmacological strategies. There are currently no consensus guidelines on management. Current and future research is aimed at identifying biomarkers and developing disease-modifying therapies.

Large‐scale mitochondrial DNA deletion underlying familial multiple system atrophy of the cerebellar subtype

“…Multiple system atrophy (MSA) is a rare adult‐onset synucleinopathy associated with dysautonomia and the variable presence of parkinsonism (MSA‐P) and/or cerebellar ataxia (MSA‐C). Magnetic resonance imaging (MRI) of the MSA‐C may show T2 hyperintensity within the Pons (hot cross bun sign), with volume loss in the Pons and cerebellum .…”

“…Multiple system atrophy (MSA) is a rare adult-onset synucleinopathy associated with dysautonomia and the variable presence of parkinsonism (MSA-P) and/or cerebellar ataxia (MSA-C). Magnetic resonance imaging (MRI) of the MSA-C may show T2 hyperintensity within the Pons (hot cross bun sign), with volume loss in the Pons and cerebellum [16,17]. A definite diagnosis of MSA-C is usually based on postmortem histological analysis of olivo-ponto-cerebellar tissue documenting glial and neuronal cytoplasmic inclusions with a-synuclein as a major component along with myelin loss [18], nevertheless the characteristic MRI brain changes and the bladder dysfunctions of our patient meet the criteria for the diagnosis of MSA-C.…”

Transcranial sonography in idiopathic REM sleep behavior disorder and multiple system atrophy

“…MSA had more widespread pathological changes and more rapid progression than PD. Increased accumulation of intracellular ferritin and reduced export of iron from the basis pontis, and to a lesser extent, the putamen, can lead to oxidative stress and mitochondrial dysfunction, which was reflected by BG hyperechogenicity . iRBD patients had BG hyperechogenicity, which represented the early changes of basal ganglia and the risk of developing MSA.…”

Alpha-synuclein in cutaneous small nerve fibers

“…Particularly, in contrast to PD, MSA has been traditionally believed to be a pure central disorder with deposition of the presumably pathological form of alpha-synuclein (phosphorilyzed alpha-synuclein) being limited to the brain and preganglionic nerve fibers 7. Consistent with this assumption, a previous investigation in skin biopsies of patients with MSA found no accumulation of the presumably pathogenic form of alpha-synuclein (phosphorylated alpha-synuclein) in cutaneous autonomic adrenergic nerve fibers 8.…”