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Patent foramen ovale, cerebrovascular risk, and complement
  1. A K Demetriades1
  1. 1The National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK
  1. Correspondence to:
 Dr A K Demetriades;
  1. K Nedeltchev2,
  2. M Arnold2,
  3. H Mattle2,
  4. S Windecker3,
  5. A Wahl3
  1. 2Department of Neurology, Inselspital, University of Bern, 3010 Bern, Switzerland
  2. 3Department of Cardiology

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    Nedeltchev et al1 report that the presence of a patent foramen ovale (PFO) is a significant risk factor for recurrent cerebrovascular events, the risk being higher in patients with more than one previous embolic event. They highlight the absence of a current proven medical treatment or prevention regimen. Cardiac right to left shunting is present in a quarter of the population. It is thus worth drawing attention to a particular subgroup of patients with PFO that may be at an even more increased risk than the authors report—sport divers, most of whom fall within the age range of the above study.

    Neurological sequelae constitute 80% of decompression sickness. Not only has neuroimaging shown an increased frequency of brain ischaemic lesions in divers, but also multiple such ischaemic lesions have been found specifically in sport divers with PFO.2 While PFO patency of haemodynamic significance is a risk factor that necessitates habit modification, often the radiological lesions do not correspond well to the neurological deficits of experienced divers.

    This point, coupled with the increased risk of arterialisation of venous bubbles and the paradoxical nature of bubble genesis, suggest that a PFO is a risk factor in this subgroup for the development of neurovascular disease.3 Unknown is the added risk with age that remains to former divers. A poorly understood mechanism of bubble induced complement involvement in the pathogenesis of the neurological sequelae in decompression sickness has been suggested.4 Similarity of such symptoms to the postcoronary bypass syndrome lends support (and hope?) to complement based neuroprotective strategy options for the future.5


    Authors' reply

    We thank Dr Demetriades for his comments on our study. While the average person with a patent foramen ovale (PFO) may not be at increased risk for neurological events, there seem to be subgroups of patients at increased risk. PFOs with large diameters, right to left shunting at rest, or high membrane mobility and PFOs associated with atrial septal aneurysms have been identified as “dangerous PFOs” by several investigators.1–3 In addition, coagulation abnormalities may promote paradoxical emboli in patients with PFO.4 To this list, Dr Demetriades adds special occupations or sports that may be dangerous in people with PFOs, specifically divers. Playing wind instruments has also been mentioned previously.5

    However, many problems related to PFO remain unresolved. Even in groups that are believed to be at high risk for neurological events, deciding whether and how to treat a PFO cannot be derived from evidence based medicine. Deciding how to proceed depends on the opinion of the attending physician and is not based on data from randomised studies.

    The PICSS (PFO in cryptogenic stroke study) showed that secondary prevention of cryptogenic stroke in patients with PFO by using warfarin or aspirin does not result in any difference.6 The PC-trial is an ongoing randomised trial we initiated to compare endovascular PFO closure versus medical treatment alone. We hope that it will provide useful information on secondary stroke prevention in patients with presumed paradoxical embolism. It is also conceivable that divers who have ever had “the bends” would benefit from PFO closure.

    Recently reported data suggest links between decompression illness, migraine with aura, and right to left shunts.8 These observations not only extend the clinical manifestations of PFO but also bring into discussion new pathophysiological aspects of migraine. If the association between complicated migraine and PFO can be corroborated, a randomised trial on PFO in such patients may be worth while.