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 <15) was used to confirm the diagnosis of mPSE. Furthermore, we evaluated the effect of lactulose administration on mPSE. Multi-slice CT, cerebral dynamic magnetic resonance, laboratory analyses and transient elastography were also used.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.