Cerebral cortical and subcortical cholinergic deficits in parkinsonian syndromes
Cerebral cortical and subcortical cholinergic deficits in parkinsonian syndromes
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DOI：
10.1212/wnl.0b013e3181dc1a55
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发表时间：
2010-05-04
期刊：
影响因子：
9.9
通讯作者：
Bhaumik, A.
中科院分区：
文献类型：
--
作者：
Gilman, S.;Koeppe, R. A.;Bhaumik, A.
目的：帕金森病（PD）的大脑皮层和皮层下区域的胆碱能投射减少，但在帕金森综合征的多系统萎缩（MSA-P）和进行性核上性麻痹（PSP）中未被评估。我们研究了这些疾病的胆碱能神经支配，并将其与适龄正常对照者进行了比较。方法：采用PET联合[(11)C]PMP检测大脑皮层及皮层下多个区域乙酰胆碱酯酶（AChE）活性。我们研究了22例正常对照，12例PD， 13例MSA-P和4例PSP。结果：我们发现PD和MSA-P的大部分大脑皮质区AChE活性显著降低，PSP的AChE活性相似但不显著降低。PD与MSA-P之间无差异。PD患者纹状体、小脑和丘脑AChE活性明显降低，中脑AChE活性轻度降低，脑桥AChE活性无变化。与PD组相比，MSA-P组和PSP组所有皮质下区域的AChE活性明显下降。3种疾病的脑干和小脑乙酰胆碱酯酶活性降低均与平衡和步态障碍相关。结论：与正常对照相比，帕金森病（PD）、帕金森多系统萎缩综合征（MSA-P）和进行性核上性麻痹（PSP）患者的大脑皮质胆碱能活性下降至相似水平。MSA-P和PSP组皮质下胆碱能活性明显低于PD组。更大幅度的下降反映了桥脑胆碱能组更大的损伤，这对运动活动，特别是步态很重要。这些差异可能解释了MSA-P和PSP早期比PD更严重的步态障碍。神经病学(R) 2010；74:1416 - 1423
Objectives: Cholinergic projections to cerebral cortical and subcortical regions are decreased in Parkinson disease (PD), but not evaluated in the parkinsonian syndromes of multiple system atrophy (MSA-P) and progressive supranuclear palsy (PSP). We studied cholinergic innervation in these disorders as compared to age-appropriate normal control subjects.Methods: We used PET with [(11)C]PMP to measure acetylcholinesterase (AChE) activity in multiple cerebral cortical and subcortical regions. We studied 22 normal controls, 12 patients with PD, 13 patients with MSA-P, and 4 patients with PSP.Results: We found significantly decreased AChE activity in most cerebral cortical regions in PD and MSA-P, and a similar but nonsignificant decrease in PSP. No differences were found between PD and MSA-P. Significantly decreased AChE activity was found in PD in striatum, cerebellum, and thalamus, with a marginally significant decrease in mesencephalon and no change in pons. Significantly greater declines in AChE activity in all subcortical regions were seen in MSA-P and PSP vs in PD. Decreased AChE activity in brainstem and cerebellum of all 3 disorders correlated with disturbances of balance and gait.Conclusions: Cerebral cortical cholinergic activity is decreased to a similar level in Parkinson disease (PD), parkinsonian syndromes of multiple system atrophy (MSA-P), and progressive supranuclear palsy (PSP) as compared to normal controls. Subcortical cholinergic activity is significantly more decreased in MSA-P and PSP than in PD. The more substantial decrease reflects greater impairment in the pontine cholinergic group, which is important in motor activity, particularly gait. These differences may account for the greater gait disturbances in the early stages of MSA-P and PSP than in PD. Neurology (R) 2010;74:1416-1423