Gastroenterology Unit, Department of Emergency and Organ Transplantation, (D.E.T.O.), University of Bari Aldo Moro, Policlinico University Hospital, Piazza G. Cesare 11, 70124 Bari, Italy.
"Frugoni" Internal Medicine Unit, Centre for Rare Diseases, Interdepartmental Centre for Hereditary Haemorrhagic Telangiectasia, Interdisciplinary Department of Medicine (D.I.M.), VascERN HHT Reference Centre, University of Bari Aldo Moro, Policlinico University Hospital, Bari, Italy.
Eur J Intern Med. 2021 Aug;90:43-48. doi: 10.1016/j.ejim.2021.04.026. Epub 2021 May 18.
Portosystemic shunts in Hereditary Haemorrhagic Telangiectasia (HHT) are often overlooked by conventional imaging although they could reduce hepatic clearance of gut-derived toxins.
To evaluate, the presence of subclinical neurological alterations (SNAs), that we named "minimal portosystemic encephalopathy" (mPSE) in HHT patients without advanced liver disease (ALD).
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-ANT) (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.
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-ANT 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-ANT 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.
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.
遗传性出血性毛细血管扩张症（HHT）中的门体分流通常会被常规影像学检查所忽略，尽管这些分流可能会降低肝脏对肠道来源毒素的清除率。
评估无晚期肝病（ALD）的 HHT 患者是否存在亚临床神经改变（SNAs），我们将其命名为“微小门体性脑病”（mPSE）。
在这项横断面研究中，我们首先通过临界闪烁频率（CFF）测试（异常值≤39Hz）对连续的 HHT 门诊患者进行筛查，并用简化动物命名测试（S-ANT）（异常值<15）来确诊 mPSE。此外，我们还评估了乳果糖给药对 mPSE 的影响。还使用了多层 CT、脑动态磁共振、实验室分析和瞬时弹性成像。
在影像学技术中，没有 37 名入组患者显示出门体分流。然而，有 33 名患者的 CFF 值正常（CFF-），4 名患者的 CFF 值异常（37.0±0.7Hz，CFF+）。S-ANT 确认 CFF+患者存在神经功能受损（10.2±2.8），从而证实存在 mPSE。值得注意的是，乳果糖给药可使这些患者的 CFF 增加（39.1±0.4Hz）和 S-ANT 正常化。无论是 mPSE-还是 mPSE+患者均无 ALD，且具有相似的人口统计学、临床和实验室参数。最后，在影像学上，没有 mPSE+患者显示出可检测到的脑血管畸形或其他脑异常。
HHT 患者是一种门体分流逃避影像学检测的微小门体性脑病的人类模型。mPSE 的评估应纳入 HHT 监测方案中，因为它可能会影响健康相关/社会方面以及经口给予的、治疗指数较窄且具有高肝脏首过摄取的药物的药代动力学。
