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• Pure Autonomic Failure: the importance of waiting to confirm the diagnosis
  Tim Young
  Published on: 17 November 2017

• Published on: 17 November 2017

  Pure Autonomic Failure: the importance of waiting to confirm the diagnosis

  • Tim Young, Consultant Neurologist Institute of Neurology

  Dear Editor,
  Thomas Brown provided a helpful recent review of pure autonomic failure (PAF) in this journal1. However, there is one very important point which I would wish to add. The diagnosis of this rare condition should be made with extreme caution in the early years of presentation. The first case in the review had a diagnosis of PAF made just two years after symptoms began. In fact, other commoner causes of primary autonomic failure may declare themselves many years after the symptoms first begin, and I have seen a number of such cases during my time at the autonomic unit in Queen Square. A rough rule of thumb used to be that at least five years should pass before making a definitive diagnosis of PAF2. More recent evidence suggests that even longer may be required. A third of cases already with symptoms suggestive of PAF for an average of 5 years were found to have an alternative diagnosis with subsequent follow up for a further four years3. Alternative diagnoses included other synucleinopathies such as Parkinson’s disease, dementia with Lewy bodies or multiple system atrophy.
  For many years attempts have been made to find reliable ways to distinguish PAF from other causes of primary autonomic failure. PAF is seen classically as a post-ganglionic disorder whilst multiple system atrophy is seen as a pre-ganglionic form of primary autonomic failure. Utilising this pathophysiological difference, a variety of differentiating tests have been attempted....

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  Dear Editor,
  Thomas Brown provided a helpful recent review of pure autonomic failure (PAF) in this journal1. However, there is one very important point which I would wish to add. The diagnosis of this rare condition should be made with extreme caution in the early years of presentation. The first case in the review had a diagnosis of PAF made just two years after symptoms began. In fact, other commoner causes of primary autonomic failure may declare themselves many years after the symptoms first begin, and I have seen a number of such cases during my time at the autonomic unit in Queen Square. A rough rule of thumb used to be that at least five years should pass before making a definitive diagnosis of PAF2. More recent evidence suggests that even longer may be required. A third of cases already with symptoms suggestive of PAF for an average of 5 years were found to have an alternative diagnosis with subsequent follow up for a further four years3. Alternative diagnoses included other synucleinopathies such as Parkinson’s disease, dementia with Lewy bodies or multiple system atrophy.
  For many years attempts have been made to find reliable ways to distinguish PAF from other causes of primary autonomic failure. PAF is seen classically as a post-ganglionic disorder whilst multiple system atrophy is seen as a pre-ganglionic form of primary autonomic failure. Utilising this pathophysiological difference, a variety of differentiating tests have been attempted. One of the more promising has been the use of functional imaging to demonstrate the cardiac sympathetic the denervation one would expect with the post-ganglionic involvement of sympathetic nerves in PAF in contrast to multiple system atrophy. However this does not distinguish PAF from Parkinson’s disease reliably. Whilst some differences in the haemodynamic responses to stimuli such as water drinking may exist between PAF and other conditions4, as yet there is not a single test which can with certainty isolate true cases of PAF from its potential mimics. These conditions can differ significantly in terms of management and prognosis. Therefore whilst a working diagnosis of PAF may be tentatively considered early in the clinical course, ongoing surveillance over many years would be an important practical suggestion in such cases.

  REFERENCES
  1 Brown TP. Pure autonomic failure. Pract Neurol. 2017 Oct;17(5):341-348

  2 Freeman R. Pure Autonomic Failure: An immaculate misconception? Neurology 2004;63;953-954

  3 Kaufmann H et al. Natural history of pure autonomic failure: A United States prospective cohort. Ann Neurol. 2017 Feb;81(2):287-297

  4 Young TM, Mathias CJ. The effects of water ingestion on orthostatic hypotension in two groups of chronic autonomic failure: multiple system atrophy and pure autonomic failure. J Neurol Neurosurg Psychiatry. 2004 Dec;75(12):1737-41.

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  Conflict of Interest:
  None declared.

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