Neurogenic orthostatic hypotension with cardiac sympathetic denervation: a potential predictor of Parkinson’s disease

Idiopathic neurogenic orthostatic hypotension (nOH) is a rare disorder of the autonomic nervous system that significantly impacts quality of life. The natural history of nOH varies and may evolve into a central synucleinopathy. Reliable and pathophysiologically relevant biomarkers of preclinical central synucleinopathies are needed. This report describes the long-term follow-up of patients with nOH and imaging evidence of cardiac sympathetic denervation using 123I-metaiodobenzylguanidine ( 123I -MIBG) single photon emission computed tomography (SPECT). Patients with orthostatic hypotension underwent clinical autonomic evaluation and were diagnosed with idiopathic nOH after excluding secondary causes. Cardiac 123I -MIBG SPECT was performed as part of the diagnostic algorithm to assess sympathetic innervation. Ten patients with nOH and cardiac sympathetic denervation were followed for the development of Parkinson’s disease (PD) or neuroimaging evidence of central dopamine deficiency using 18 F-DOPA positron emission tomography (PET). During a mean follow-up of 5.6 years, most patients showed clinical or neuroimaging signs of central dopamine deficiency: Seven were diagnosed with Parkinson’s disease; three showed non-diagnostic minimal extrapyramidal signs, among which two had unilaterally reduced 18 F-DOPA -uptake. Among five patients tested for genetic mutations related to Parkinson’s disease, four were GBA mutation carriers. In this cohort, the vast majority of patients with nOH and imaging evidence of cardiac sympathetic denervation progressed to Parkinson’s disease during follow-up, with most of the remainder developing clinical or neuroimaging evidence of nigrostriatal dopamine deficiency. This form of nOH appears to represent a body-first course toward Parkinson’s disease via the sympathetic route.