Non-motor symptoms in multiple system atrophy: A comparative study with Parkinson's disease and progressive supranuclear palsy

Abstract

BackgroundNon-motor symptoms (NMS) are compulsory clinical features for the clinical diagnosis of multiple system atrophy (MSA), some of which precede motor symptoms onset. To date, few studies have systematically investigated NMS in MSA and the timing of presenting NMS as the disease progresses. Clinically, MSA is difficult to be differentiated from Parkinson's disease (PD) and progressive supranuclear palsy (PSP), and the differences in NMS between MSA and PD/PSP remain unclear. The aim of this study was to compare the burden of NMS between MSA and PD/PSP and to delineate the timing of NMS presentation relative to the onset of motor symptoms in MSA.MethodsA total of 61, 87, and 30 patients with MSA, PD, and PSP, respectively, were enrolled in this study. NMS was systematically assessed in all patients using the NMS scale (NMSS), and the onset of NMS relative to the onset of motor symptoms in MSA was investigated.ResultsMSA group had higher total NMSS scores (82.15 ± 46.10) than the PD (36.14 ± 30.78) and PSP (50.30 ± 55.05) groups (p < 0.001 overall). The number distribution pattern of the NMS was significantly different among the three parkinsonian disorders (p < 0.001 overall). In total, 85.2% of patients with MSA had more than 10 NMS, which was significantly higher than PD (28.7%) and PSP (33.3%). The frequency and scores of many NMSS subdomains and symptoms were higher in MSA than in PD and PSP (all p < 0.05). Multivariate logistic regression analysis revealed that patients with fainting, lack of motivation, swallowing, and loss of sexual interest could be attributed to MSA rather than PD or PSP, while patients with loss of concentration and forgetfulness were characteristic features of PD or PSP rather than MSA. REM-sleep behavior disorder (RBD), constipation, problems having sex, and loss of sexual interest preceded the motor symptoms onset of MSA by 2.81 ± 4.51, 1.54 ± 6.32, 1.35 ± 4.70, and 0.45 ± 3.61 years, respectively.ConclusionThe NMS spectrum in MSA differs from that of PD and PSP. Patients with MSA have a higher NMS burden than patients with PD or PSP. RBD, constipation, problems having sex, and loss of sexual interest may become early diagnostic clinical markers of MSA.

Sex-related differences in the clinical presentation of multiple system atrophy

“…The literature on sex-related differences in the clinical presentation of MSA suggested that compared to men, women more frequently have a motor symptomatic onset and a better response to L-dopa, but overall develop greater motor disability over time and more frequently suffer from pain, depression, anxiety, sarcopenia, frailty, early falls, fractures, worse cognitive performance, and lower health-related quality of life [ 10 , 11 , 22 , 25 , 31 , 48 , 50 , 51 , 59 ]. By contrast, men were more frequently reported to have an autonomic symptomatic onset and to suffer from more widespread and severe autonomic failure, except for urinary urge incontinence and constipation, which were more common in women [ 10 , 12 , 20 , 34 , 36 , 37 , 41 , 51 , 55 , 60 , 61 ]. Higher supine BP levels as well as greater orthostatic BP falls were both associated with increased mortality in men with MSA [ 54 , 57 ].…”

“…The literature on sex-related differences in the clinical presentation of MSA primarily consisted of studies conducted following the publication of the second consensus MSA criteria [ 14 ]. Altogether, these studies indicated that women suffer from a greater motor disability and higher neuropsychiatric burden, while possibly experiencing a slight survival benefit due to initial motor onset and overall less severe autonomic failure compared to men [ 10 – 12 , 38 , 41 , 51 , 52 , 54 , 55 , 57 , 60 , 61 ]. A motor onset in MSA may positively impact women’s survival by prompting an earlier referral, diagnosis, and thus optimized care [ 10 ].…”

Predicting the Prognosis of Multiple System Atrophy Using Cluster and Principal Component Analysis

“…Multiple system atrophy (MSA) is an intractable neurodegenerative disorder characterized by various combinations of parkinsonism, cerebellar ataxia, and autonomic failure, and the prevalence of MSA is 3–5/100000 in the general population [ 1 , 2 ]. Two main subtypes of MSA are MSA with predominant parkinsonism (MSA-P) and MSA with prominent cerebellar ataxia (MSA-C).…”