Standing upright is complex business and requires a finely tuned set of reflex responses. If these reflex responses fail, blood pressure plummets, blood supply to the brain is cut off, and sooner or later we all fall down.

When the nerves that control the blood vessels are damaged, falls in blood pressure occur each time we stand. This condition – known as orthostatic hypotension – can indicate something more troubling. Evidence is piling up to show that patients with orthostatic hypotension have a much greater risk of developing synucleinopathies – like Parkinson disease and multiple system atrophy. These diseases are caused by the abnormal accumulation of the misfolded protein alpha-synuclein and its prion-like spread to areas of the brain that control movement and cognition.

Orthostatic hypotension can – at times – be difficult to diagnose. Current guidelines teach us, we should measure the blood pressure lying down and see if it falls after 3 minutes of standing. But, not every patient encountered in the clinic meets the 3-minute criteria. Some have what is now known as delayed orthostatic hypotension, and require longer than 3 minutes standing to drop their blood pressure.

As Dr. Kaufman points out, delayed orthostatic hypotension is not a trivial issue. In this issue of Neurology our Autonomic Consortium collaborators in Boston published an article describing the follow-up of their patients with delayed orthostatic hypotension. Within 10-years, blood pressure control gets progressively worse in these patients. But, perhaps most worrisome, is that one-third of patients with delayed orthostatic hypotension, then go on to develop synucleinopathies and signs of brain disease.

Both the article and the editorial suggest that we might need to have more patience with our patients. There may be virtue in waiting more that 3 minutes to detect a fall in blood pressure standing. Autonomic features are now being recognized as early signs of abnormal alpha-synuclein accumulation in the body. Diagnosing this in the pre-motor phase may present a unique therapeutic window – and a chance to intervene early to stop the spread of the disease to the brain.

Read the article here: Gibbons CH, Freeman R. Clinical implications of delayed orthostatic hypotension: A 10-year follow-up study. Neurology. 2015 Sep 23. [Epub ahead of print] PMID: 26400576

Read the editorial here: Kaufmann H, Jacobs G. Early and delayed orthostatic hypotension: Time tells. Neurology. 2015.