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Primary determinants of ischaemic stroke/brain abscess risks are independent of severity of pulmonary arteriovenous malformations in HHT
  1. Claire Shovlin (c.shovlin{at}ic.ac.uk)
  1. Imperial college, United Kingdom
    1. James Jackson (jejackson{at}hhnt.nhs.uk)
    1. Hammesrmith Hospital, United Kingdom
      1. Kathleen Bamford (k.bamford{at}imperial.ac.uk)
      1. Imperial, United Kingdom
        1. Harri Jenkins (harri.jenkins{at}imperial.ac.uk)
        1. Imperial, United Kingdom
          1. Andrea Benjamin (andreabenjamin{at}yahoo.com)
          1. Hammersmith, United Kingdom
            1. Hatem Ramadan (hkhk00{at}hotmail.com)
            1. Hammersmith, United Kingdom
              1. Elena Kulinskaya (e.kulinskaya{at}imperial.ac.uk)
              1. Imperial, United Kingdom

                Abstract

                Background: Brain abscesses and ischaemic strokes complicate pulmonary arteriovenous malformations (PAVMs). At-risk individuals are poorly recognised. Stroke/abscess risk factors have not been defined.

                Methods: A cohort study of 323 consecutive individuals with PAVMs (n=219) and/or the commonly associated condition hereditary haemorrhagic telangiectasia (HHT, n=305) was performed. Most of the 201 individuals with PAVMs and HHT had no respiratory symptoms, and were unaware they had HHT. Anderson-Gill models assessed constant and time-dependent potential predictive variables for stroke/abscess, and rate-reduction by PAVM embolisation.

                Results: Fifty-seven individuals with PAVMs and HHT experienced brain abscess or ischaemic stroke, usually prior to the diagnosis of underlying PAVMs/HHT. The primary determinants of stroke and abscess risks were unrelated to severity of PAVMs: Males had higher brain abscess rates (hazard ratio 3.61 (95% CI 1.58, 8.25), p=0.0024): interventional histories and bacteriological isolates suggested dental sources. Once adjusted for gender, there was a marginal association between brain abscess and low oxygen saturation. For ischaemic stroke, there was no association with severity of any marker of PAVM severity, nor with conventional neurovascular risk factors. Surprisingly, low mean pulmonary artery pressure was strongly associated with ischaemic stroke (hazard ratio 0.89 (95% CI 0.83, 0.95) per mmHg increase, p=6.2x10-5). PAVM embolisation significantly reduced ischemic stroke rate (p=0.028); no strokes/abscesses occurred following obliteration of all angiographically visible PAVMs. The mean PAVM diagnosis-treatment interval was longer however, when neurological risks were unrecognised.

                Conclusions: Ischaemic strokes and brain abscesses occur commonly in undiagnosed HHT patients with PAVMs. Risk reduction could be improved.

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