Department of Neurology, Beth Israel Medical Center, NY 10003, USA.
Parkinsonism Relat Disord. 2013 Feb;19(2):186-91. doi: 10.1016/j.parkreldis.2012.09.007. Epub 2012 Oct 10.
Heterozygous glucocerebrosidase (GBA) mutations are the leading genetic risk factor for Parkinson disease, yet imaging correlates, particularly transcranial sonography, have not been extensively described.
To determine whether GBA mutation heterozygotes with Parkinson disease demonstrate hyperechogenicity of the substantia nigra, transcranial sonography was performed in Ashkenazi Jewish Parkinson disease subjects, tested for the eight most common Gaucher disease mutations and the LRRK2 G2019S mutation, and in controls. [(18)F]-fluorodeoxyglucose or [(18)F]-fluorodopa positron emission tomography is also reported from a subset of Parkinson disease subjects with heterozygous GBA mutations.
Parkinson disease subjects with heterozygous GBA mutations (n = 23) had a greater median maximal area of substantia nigral echogenicity compared to controls (n = 34, aSNmax = 0.30 vs. 0.18, p = 0.007). There was no difference in median maximal area of nigral echogenicity between Parkinson disease groups defined by GBA and LRRK2 genotype: GBA heterozygotes; GBA homozygotes/compound heterozygotes (n = 4, aSNmax = 0.27); subjects without LRRK2 or GBA mutations (n = 32, aSNmax = 0.27); LRRK2 heterozygotes/homozygotes without GBA mutations (n = 27, aSNmax = 0.28); and GBA heterozygotes/LRRK2 heterozygotes (n = 4, aSNmax = 0.32, overall p = 0.63). In secondary analyses among Parkinson disease subjects with GBA mutations, maximal area of nigral echogenicity did not differ based on GBA mutation severity or mutation number. [(18)F]-fluorodeoxyglucose (n = 3) and [(18)F]-fluorodopa (n = 2) positron emission tomography in Parkinson disease subjects with heterozygous GBA mutations was consistent with findings in idiopathic Parkinson disease.
Both transcranial sonography and positron emission tomography are abnormal in GBA mutation associated Parkinson disease, similar to other Parkinson disease subjects.
杂合型葡萄糖脑苷脂酶（GBA）突变是帕金森病的主要遗传风险因素，但影像学相关性，特别是经颅超声检查，尚未得到广泛描述。
为了确定是否 GBA 突变杂合子帕金森病患者的黑质回声增强，对阿什肯纳兹犹太帕金森病患者进行了经颅超声检查，这些患者检测了 8 种最常见的戈谢病突变和 LRRK2 G2019S 突变，并对对照组进行了检测。还报告了一部分 GBA 突变杂合子帕金森病患者的 [(18)F]-氟脱氧葡萄糖或 [(18)F]-氟多巴正电子发射断层扫描。
与对照组相比，GBA 突变杂合子帕金森病患者（n=23）的黑质最大回声面积中位数更大（aSNmax=0.30 比 0.18，p=0.007）。根据 GBA 和 LRRK2 基因型定义的帕金森病组之间，黑质回声面积中位数无差异：GBA 杂合子；GBA 纯合子/复合杂合子（n=4，aSNmax=0.27）；无 LRRK2 或 GBA 突变的患者（n=32，aSNmax=0.27）；LRRK2 杂合子/无 GBA 突变的纯合子（n=27，aSNmax=0.28）；以及 GBA 杂合子/ LRRK2 杂合子（n=4，aSNmax=0.32，总体 p=0.63）。在 GBA 突变帕金森病患者的次要分析中，黑质回声面积的最大值不因 GBA 突变严重程度或突变数量而异。在 GBA 突变杂合子帕金森病患者中进行的 [(18)F]-氟脱氧葡萄糖（n=3）和 [(18)F]-氟多巴（n=2）正电子发射断层扫描与特发性帕金森病的结果一致。
经颅超声和正电子发射断层扫描在 GBA 突变相关的帕金森病中均异常，与其他帕金森病患者相似。
