Minimal portosystemic encephalopathy: A new nosological entity in patients with hereditary haemorrhagic telangiectasia

Background. Portosystemic shunts in Hereditary Haemorrhagic Telangiectasia (HHT) are often overlooked by conventional imaging although they could reduce hepatic clearance of gut-derived toxins. Aims. To evaluate, the presence of subclinical neurological alterations (SNAs), that we named “minimal portosystemic encephalopathy” (mPSE) in HHT patients without advanced liver disease (ALD). Methods. In this cross sectional study, consecutive HHT outpatients were firstly screened by critical flicker frequency (CFF) test (abnormal ≤39Hz), and the simplified animal naming test (S-ANT1) (abnormal Results. None of the 37 enrolled patients showed portosystemic shunts at imaging techniques. However, 33 patients had normal CFF values (CFF-) and 4 displayed CFF alterations (37.0±0.7Hz, CFF+). The S-ANT1 confirmed an impaired neurological performance (10.2±2.8) in CFF+ patients thus confirming the presence of mPSE. Noteworthy, lactulose administration determined a CFF increase (39.1±0.4Hz) and S-ANT1 normalization in these patients. Neither mPSE- nor mPSE+ patients had ALD and showed similar demographic, clinical and laboratory parameters. Finally, no mPSE+ patient showed radiologically-detectable brain vascular malformations or other brain abnormalities at imaging. Conclusions. HHT patients represent a human model of mPSE secondary to portosystemic shunts escaping radiological detection. mPSE evaluation should be incorporated in HHT surveillance protocols since it can affect both health-related/social aspects and pharmacokinetics of orally administered drugs with a narrow therapeutic index and high hepatic first-pass uptake.