Mueller Antje, Reuner Ulrike, Landis Basile, Kitzler Hagen, Reichmann Heinz, Hummel Thomas
Smell & Taste Clinic, Department of Otorhinolaryngology, University of Dresden Medical School, Dresden, Germany.
Mov Disord. 2006 Sep;21(9):1311-6. doi: 10.1002/mds.20989.
Wilson's disease is a rare autosomal recessive disorder characterized by the accumulation of copper, mainly in the liver and the brain. As copper accumulation in the brain leads to disturbances in basal ganglia function, neurological-type patients typically present with hypo- and hyperkinetic extrapyramidal symptoms, with Parkinsonism being very common. Although there are numerous reports on olfactory deficits in primary neurodegenerative disorders, olfactory function has not been investigated in metabolic disorders presenting with extrapyramidal features. Twenty-four patients with Wilson's disease participated in the investigation. All patients were treated pharmacologically. They comprised patients with liver disease alone (including mild enzyme elevation in asymptomatic individuals; n = 11) and/or neurological symptoms (n = 13) at the time of testing. Twenty-one patients underwent both [18F]fluoro-2-deoxy-D-glucose positron emission tomography ([18F]FDG-PET) and magnetic resonance imaging (MRI). The severity of extrapyramidal symptoms was judged using a clinical score system ranging from 0 (no symptoms) to 3 (severe symptoms). In all patients, psychophysical testing was performed using the Sniffin' Sticks, which involved tests for odor threshold, discrimination, and identification. Results from the present study revealed that Wilson's disease patients with neurological symptoms show a significant olfactory dysfunction compared to hepatic-type patients. Individuals who are more severely neurologically affected also present with a more pronounced olfactory deficit. Of interest, there was no significant effect of long-term treatment with penicillamine on olfactory function. Olfactory function did not correlate significantly with the presence of MRI visible lesions in the basal ganglia or with any regional glucose metabolism as measured by [18]F-FDG-PET. In conclusion, these findings indicate that the underlying pathological alterations with degeneration in the basal ganglia and neuronal loss in association with a marked increase of the copper content in this brain region play a role in the olfactory deficit.
威尔逊病是一种罕见的常染色体隐性疾病，其特征是铜的蓄积，主要在肝脏和大脑中。由于大脑中铜的蓄积会导致基底神经节功能紊乱，神经型患者通常表现为运动减少和运动增多的锥体外系症状，其中帕金森综合征非常常见。尽管有许多关于原发性神经退行性疾病嗅觉缺陷的报道，但尚未对具有锥体外系特征的代谢性疾病的嗅觉功能进行研究。24例威尔逊病患者参与了该研究。所有患者均接受了药物治疗。在测试时，他们包括仅患有肝病的患者（包括无症状个体的轻度酶升高；n = 11）和/或有神经症状的患者（n = 13）。21例患者接受了[18F]氟-2-脱氧-D-葡萄糖正电子发射断层扫描（[18F]FDG-PET）和磁共振成像（MRI）。使用从0（无症状）到3（严重症状）的临床评分系统来判断锥体外系症状的严重程度。在所有患者中，使用嗅觉棒进行了心理物理学测试，该测试包括气味阈值、辨别和识别测试。本研究结果显示，与肝型患者相比，有神经症状的威尔逊病患者存在明显的嗅觉功能障碍。神经受累更严重的个体也表现出更明显的嗅觉缺陷。有趣的是，青霉胺长期治疗对嗅觉功能没有显著影响。嗅觉功能与基底神经节MRI可见病变的存在或[18F]FDG-PET测量的任何区域葡萄糖代谢均无显著相关性。总之，这些发现表明，基底神经节变性和神经元丢失以及该脑区铜含量显著增加的潜在病理改变在嗅觉缺陷中起作用。
