Serra M M, Besada C H, Cabana Cal A, Saenz A, Stefani C V, Bauso D, Golimstok A B, Bandi J C, Giunta D H, Elizondo C M
Internal Medicine Department. Hospital Italiano de Buenos Aires. Argentina (HIBA), Presidente Perón 4190, Cuidad Autónoma de Buenos Aires, C1199ABB, Argentina.
HHT Unit. Hospital Italiano de Buenos Aires, Ciudad Autonoma de Buenos Aires, Argentina.
Orphanet J Rare Dis. 2017 May 18;12(1):92. doi: 10.1186/s13023-017-0632-2.
Around 47-74% of patients with hereditary hemorrhagic telangiectasia (HHT) have hepatic vascular malformations (HVMs); magnetic resonance images (MRI) of the central nervous system (CNS) might show in T1 sequences a hyper-intensity signal in different areas, mainly in the basal ganglia (BG) as consequence of manganese (Mn) deposits as observed in cirrhotic patients. These patients might suffer from different neuropsychiatric disorders (hepatic encephalopathy). In HHT patients, even in the presence of hepatic shunts, hepatocellular function is usually preserved. Additionally, Mn shares iron absorption mechanisms, transferrin and CNS transferrin receptors. In iron deficiency conditions, the Mn may harbor transferrin and access BG. The objectives were to describe frequency of BG Mn deposit-induced lesions (BGMnIL) in HHT patients, its relationship with iron deficiency anemia (IDA) and HVMs. Finally, explore the association between neuropsychological and motor consequences. We performed a cross-sectional study. We determined HHT patients with or without BG-MnIL by the MRI screening of the CNS. We included all patients with lesions and a random sample of those without lesions. All patients underwent standardized and validated neuropsychological assessment to evaluate BG actions. Results were analyzed with multiple logistic regression, adjusting for potential confounders.
Among 307 participants from a cohort included in the Institutional HHT Registry, 179 patients had MRI performed and Curaçao Criteria ≥3. The prevalence of BG-MnIL was 34.6% (95%CI 27.69-42.09). While neuropsychological symptoms were present in all patients, BG-MnIL patients performed poorly in three of the neuropsychological tests (serial dotting, line tracing time, number connection test A). HVMs frequency in BG-MnIL was 95.1%, versus 71.4% in those without lesions (p < 0.001). IDA frequency was 90.3% versus 54% (p < 0.001). When IDA is present, estimated risk for BG-MnIL is remarkably high (OR 7.73, 95%CI 2.23-26.73). After adjustment for possible confounders (gender, age, presence of HVMs), IDA was still associated with increased risk of BG-MnIL (adjusted OR 6.32, 95% CI 2.32-17.20; p < 0.001).
Physicians should assess BG-MnIL in HHT patients in CNS-MRI. IDA and HVMs present increased risk of lesions. Patients with BG-MnIL have neuropsychological impairment, and they might benefit from sparing IDA, or undergoing future therapeutic options.
NCT01761981 . Registered January 3 2013.
遗传性出血性毛细血管扩张症（HHT）患者中约47%-74%有肝血管畸形（HVM）；中枢神经系统（CNS）的磁共振成像（MRI）在T1序列中可能显示不同区域出现高强度信号，主要在基底神经节（BG），这是由于肝硬化患者中观察到的锰（Mn）沉积所致。这些患者可能患有不同的神经精神障碍（肝性脑病）。在HHT患者中，即使存在肝分流，肝细胞功能通常也能保留。此外，锰与铁的吸收机制、转铁蛋白和中枢神经系统转铁蛋白受体相同。在缺铁情况下，锰可能与转铁蛋白结合并进入基底神经节。目的是描述HHT患者中基底神经节锰沉积诱导性病变（BGMnIL）的发生率、其与缺铁性贫血（IDA）和HVM的关系。最后，探讨神经心理和运动后果之间的关联。我们进行了一项横断面研究。通过对中枢神经系统的MRI筛查确定有或无BGMnIL的HHT患者。我们纳入了所有有病变的患者以及无病变患者的随机样本。所有患者均接受标准化且经过验证的神经心理评估以评估基底神经节功能。对结果进行多因素逻辑回归分析，并对潜在混杂因素进行校正。
在机构HHT登记处队列的307名参与者中，179名患者进行了MRI检查且符合库拉索标准≥3。BGMnIL的患病率为34.6%（95%CI 27.69-42.09）。虽然所有患者都有神经心理症状，但BGMnIL患者在三项神经心理测试（连续点计数、线追踪时间、数字连接测试A）中表现不佳。BGMnIL患者中HVM的发生率为95.1%，而无病变患者中为71.4%（p<0.001）。IDA的发生率为90.3%，而无病变患者中为54%（p<0.001）。当存在IDA时，BGMnIL的估计风险非常高（OR 7.73，95%CI 2.23-26.73）。在对可能的混杂因素（性别、年龄、HVM的存在）进行校正后，IDA仍然与BGMnIL风险增加相关（校正OR 6.32，95%CI 2.32-17.20；p<0.001）。
医生应在中枢神经系统MRI中评估HHT患者的BGMnIL。IDA和HVM会增加病变风险。患有BGMnIL的患者存在神经心理损害，他们可能会从避免IDA或接受未来的治疗选择中受益。
NCT01761981。于2013年1月3日注册。
