Premotor signs and symptoms of multiple system atrophy

Differential Progression of Dysphagia in Heredity and Sporadic Ataxias Involving Multiple Systems

“…Swallowing is a complex activity involving many sensory and motor nuclei in the brainstem. A pathological study reported that the solitary nucleus, a viscerosensory nucleus associated with swallowing, cardiovascular regulation, and respiration, was affected in MSA [20]. In contrast, another report described that neurodegeneration of the solitary nuclei was relatively mild in SCA3, as compared with other nuclei including the ambiguus nucleus [21], a visceromotor nucleus also severely affected in MSA [22].…”

Atypical Parkinsonism

“…56,57 Urogenital dysfunction precedes orthostatic hypotension in most patients. 56,58,59 Erectile dysfunction, which may precede the onset of urinary symptoms, occurs in up to 97% of men with definite MSA and is reported as the first symptom in up to 48% of patients. 56,58 For female patients, sexual dysfunction is more difficult to assess; therefore, data are missing.…”

“…Central sleep apnea is less common and tends to occur at later stages. 58,[63][64][65][66] Other clinical features and "red flags" REM sleep behavior disorder (RBD) is very common in MSA and, together with autonomic dysfunction, represents a premotor stage in MSA in many patients and should alert for diagnosis. RBD is also seen, but less frequently, in PD and quite rarely in PSP.…”

“…RBD is also seen, but less frequently, in PD and quite rarely in PSP. 56,58,[67][68][69][70][71] Early falls and postural instability, also seen in PSP, may also be a feature of MSA and can cause diagnostic difficulties with PSP. Careful examination of eye movement abnormalities and early frontal-subcortical dysfunction which is common in PSP but not in MSA, will aid the diagnosis.…”

Animal Models of Multiple-System Atrophy

“…MSA neuropathology is characterized by: (1) selective striatonigral degeneration (SND) and/or olivopontocerebellar atrophy (OPCA), accompanied by neurodegeneration in autonomic centers; (2) the hallmark of the disease-widespread a-synuclein (aSyn) positive oligodendroglial cytoplasmic inclusions (GCIs) along with less common neuronal cytoplasmic (NCIs) and neuronal or glial nuclear inclusions (NNIs, GNIs); and, finally, (3) astrogliosis and microgliosis which accompany the neurodegeneration and the a-synucleinopathy in MSA brains. Importantly, the applicability of MSA models for preclinical target validation is strengthened by functional outcome measures of progression, which would replicate the clinical features of the disease: (1) motor syndromes related to SND (parkinsonism) and OPCA (ataxia), as well as (2) non-motor presentation, including cardiovascular, urogenital, respiratory, gastrointestinal, sudomotor, and sleep disorders [1][2][3].…”