To investigate if the upper motor neuron (UMN) signs in multiple system atrophy (MSA) is associated with other characteristic features. 

The diagnosis of MSA is based on four clinical domains: autonomic, parkinsonism, cerebellar, and corticospinal tract symptoms and signs. However, the involvement of corticospinal tract, manifesting as UMN symptoms, is poorly understood in MSA.  

We reviewed 40 autopsy-confirmed MSA cases from New York Brain Bank and assessed the UMN signs. The overall UMN burden score was 0-36, calculated by scoring deep tendon reflexes, muscle tone, and pyramidal signs. MSA patients were divided into those with high UMN burden (HUMN) ≥ 18 and low UMN < 18 (LUMN). We compared the clinical characteristics of MSA patients with HUMN vs.LUMN using Chi-Square and independent t test. We investigated if UMN burden is associated with the presence of autonomic, parkinsonism, and cerebellar features. We conducted a multivariable linear regression to examine if UMN burden is associated with survival. 

MSA cases with HUMN (37%, n = 15) and those with LUMN (63%, n = 25) have similar age, sex, age of onset, and disease duration. MSA cases with HUMN are more likely to be MSA-P than those with LUMN (p = 0.03). MSA patients with HUMN are more likely to have urinary incontinence (Odds Ratio = 4.13, p = 0.041) but less likely to have rapid eye movement behavioral sleep disorders (Odds Ratio = 0.13, p = 0.038). The HUMN subjects do not differ from those with LUMN in regards to bowel dysfunction, orthostatic hypotension, stridor, or dry eyes. Patients with HUMN and those with LUMN are not different in survival. 

UMN symptoms are associated with different MSA subtypes and autonomic features. Further studies are needed to fully characterize this often-neglected clinical domain for MSA.