Autonomic function and non-motor symptoms in primary chronic autonomic failure disorders

Abstract

The autonomic nervous system innervates and influences every organ in the body through two major efferent pathways; the sympathetic and parasympathetic nervous systems. Autonomic dysfunction, especially orthostatic hypotension (OH) and olfactory dysfunction, are commonly present in a variety of neurological disorders, particularly, multiple system atrophy (MSA) and allied disorders, such as Parkinson’s disease (PD) and Pure Autonomic Failure (PAF) and can significantly impact quality of life and cause significant morbidity. Similarly, non-motor symptoms have been increasingly recognized in PD. The overlapping autonomic features of PD, PAF and MSA, e.g., OH, can sometimes make it difficult to differentiate a diagnosis between these conditions. The further evaluation of autonomic function, e.g., cardiovascular, olfactory and gastrointestinal function, in patients with primary chronic autonomic failure disorders could offer better diagnostic accuracy, improve the understanding of disease progression and inform the development of treatments. Cardiovascular autonomic function screening tests are commonly used to confirm a diagnosis of autonomic failure, e.g., orthostatic hypotension, but OH is not often reliable for distinguishing between PD and MSA. Novel indices of cardiovascular autonomic function in patients with chronic autonomic failure have therefore been evaluated as well as the severity of olfactory dysfunction and other non-motor (e.g., daily activities and depression) symptoms in MSA, PD and PAF. Results demonstrated that baroreflex sensitivity and blood pressure recovery time (BRPT) in response to the Valsalva Manoeuvre are useful for differentiating MSA from PD with autonomic failure (PD+AF). BPRT was also significantly prolonged in PD patients compared to healthy controls. In addition, an association of BPRT and disease duration in PD also suggests that this index may be useful for monitoring disease progression in PD. Other findings indicated that assessing olfactory function is also helpful for distinguishing between PD, MSA and PAF. A greater degree of depression and impairment of daily activities in MSA relative to PD and PAF were also evident. In order to further investigate the presenting symptoms and features of PAF, a time when diagnosis is often still unclear, and other disorders, such as MSA, can be suspected, the clinical characteristics and laboratory investigations, in a large cohort of PAF patients were examined. Results indicated that abnormal white matter lesions are prevalent in PAF. Furthermore, gastrointestinal symptoms were also evident in PAF and can also occur in other autonomic disorders, e.g., MSA. Using electrogastrography, impaired indexes of gastric motility were also evident in PAF.