■在多系统萎缩伴显性帕金森病(MSA-P)的典型患者中,左旋多巴无效。然而,其中一些患者对左旋多巴治疗反应良好。左旋多巴在MSA-P患者中的疗效被认为与壳损伤程度有关,但是尚未详细确定putaminal受累与左旋多巴疗效之间的病理原因。
■本研究旨在评估“左旋多巴反应性”MSA-P患者与“左旋多巴无反应性”常规MSA-P患者的黑质纹状体多巴胺能系统的神经病理学特征。
■对一名53岁的日本MSA患者进行了临床病理评估,该患者表现为不对称帕金森病,左旋多巴反应,以及后来的磨损现象。在尸检期间,研究了突触前和突触后多巴胺能受体密度和α-突触核蛋白状态的黑质纹状体病理学。使用相同的病理方案检查了其他两名MSA-P患者。
■发病四年后,患者死于突然的心肺骤停。尸检时,基底神经节中大量α-突触核蛋白阳性神经胶质细胞质包涵体,pons,和小脑被确认。壳核中的神经元数量和多巴胺受体的免疫反应性得到了很好的保留。相比之下,在“左旋多巴无反应的”MSA-P对照患者中,观察到壳核中神经元的显着丢失和多巴胺受体免疫反应性降低。这些推定病理结果与死前磁共振成像(MRI)的发现一致。所有三名患者同样表现出黑质中严重的神经元丢失和多巴胺转运蛋白的免疫反应性降低。
■MSA-P患者的左旋多巴反应性可能由MRI上正常的壳核和病理检查上保留的突触后黑质纹状体多巴胺能系统证实。这项研究的结果可能为诊断为MSA-P的患者继续使用左旋多巴治疗提供依据。
UNASSIGNED: In typical patients with multiple system atrophy with predominant parkinsonism (MSA-P)
levodopa is ineffective. However, there are some of these patients who respond well to
levodopa treatment.
Levodopa efficacy in MSA-P patients is thought to be related to the degree of putaminal damage, but the pathological causation between the putaminal involvement and
levodopa efficacy has not been established in detail.
UNASSIGNED: This study aimed to evaluate the neuropathological features of the nigrostriatal dopaminergic system in a \"levodopa-responsive\" MSA-P patient in comparison with \"
levodopa-unresponsive\" conventional MSA-P patients.
UNASSIGNED: Clinicopathological findings were assessed in a 53-year-old Japanese man with MSA who presented with asymmetric parkinsonism, levodopa response, and later wearing-off phenomenon. During autopsy, the nigrostriatal pathology of presynaptic and postsynaptic dopaminergic receptor density and α-synuclein status were investigated. The other two patients with MSA-P were examined using the same pathological protocol.
UNASSIGNED: Four years after the onset, the patient died of sudden cardiopulmonary arrest. On autopsy, numerous α-synuclein-positive glial cytoplasmic inclusions in the basal ganglia, pons, and cerebellum were identified. The number of neurons in the putamen and immunoreactivity for dopamine receptors were well-preserved. In contrast, significant neuronal loss and decreased dopamine receptor immunoreactivity in the putamen were observed in the \"levodopa-unresponsive\" MSA-P control patients. These putaminal pathology results were consistent with the findings of premortem magnetic resonance imaging (MRI). All three patients similarly exhibited severe neuronal loss in the substantia nigra and decreased immunoreactivity for dopamine transporter.
UNASSIGNED: Levodopa responsiveness in patients with MSA-P may be corroborated by the normal putamen on MRI and the preserved postsynaptic nigrostriatal dopaminergic system on pathological examination. The results presented in this study may provide a rationale for continuation of levodopa treatment in patients diagnosed with MSA-P.