Neuropathological features of levodopa-responsive parkinsonism in multiple system atrophy: an autopsy case report and comparative neuropathological study
BackgroundIn 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,...
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2023.1293732/full |
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| author | Mitsuyoshi Tamura Takahiro Takeda Yoshihisa Kitayama Tomoki Suichi Kazumoto Shibuya Sakurako Harada-Kagitani Takashi Kishimoto Satoshi Kuwabara Shigeki Hirano |
| author_facet | Mitsuyoshi Tamura Takahiro Takeda Yoshihisa Kitayama Tomoki Suichi Kazumoto Shibuya Sakurako Harada-Kagitani Takashi Kishimoto Satoshi Kuwabara Shigeki Hirano |
| author_sort | Mitsuyoshi Tamura |
| collection | DOAJ |
| description | BackgroundIn 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.ObjectiveThis 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.Materials and methodsClinicopathological 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.ResultsFour 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.ConclusionLevodopa 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. |
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| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-03-11T10:36:37Z |
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| spelling | doaj.art-8ade0e42a3c84d4e977925c388acc9f72023-11-14T10:22:58ZengFrontiers Media S.A.Frontiers in Neurology1664-22952023-11-011410.3389/fneur.2023.12937321293732Neuropathological features of levodopa-responsive parkinsonism in multiple system atrophy: an autopsy case report and comparative neuropathological studyMitsuyoshi Tamura0Takahiro Takeda1Yoshihisa Kitayama2Tomoki Suichi3Kazumoto Shibuya4Sakurako Harada-Kagitani5Takashi Kishimoto6Satoshi Kuwabara7Shigeki Hirano8Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, JapanDepartment of Neurology, National Hospital Organization Chiba Higashi Hospital, Chiba, JapanDepartment of Neurology, Graduate School of Medicine, Chiba University, Chiba, JapanDepartment of Neurology, Graduate School of Medicine, Chiba University, Chiba, JapanDepartment of Neurology, Graduate School of Medicine, Chiba University, Chiba, JapanDepartment of Molecular Pathology, Graduate School of Medicine, Chiba University, Chiba, JapanDepartment of Molecular Pathology, Graduate School of Medicine, Chiba University, Chiba, JapanDepartment of Neurology, Graduate School of Medicine, Chiba University, Chiba, JapanDepartment of Neurology, Graduate School of Medicine, Chiba University, Chiba, JapanBackgroundIn 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.ObjectiveThis 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.Materials and methodsClinicopathological 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.ResultsFour 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.ConclusionLevodopa 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.https://www.frontiersin.org/articles/10.3389/fneur.2023.1293732/fullmultiple system atrophylevodopaputamenpathologypresynaptic dopaminergic fibers |
| spellingShingle | Mitsuyoshi Tamura Takahiro Takeda Yoshihisa Kitayama Tomoki Suichi Kazumoto Shibuya Sakurako Harada-Kagitani Takashi Kishimoto Satoshi Kuwabara Shigeki Hirano Neuropathological features of levodopa-responsive parkinsonism in multiple system atrophy: an autopsy case report and comparative neuropathological study Frontiers in Neurology multiple system atrophy levodopa putamen pathology presynaptic dopaminergic fibers |
| title | Neuropathological features of levodopa-responsive parkinsonism in multiple system atrophy: an autopsy case report and comparative neuropathological study |
| title_full | Neuropathological features of levodopa-responsive parkinsonism in multiple system atrophy: an autopsy case report and comparative neuropathological study |
| title_fullStr | Neuropathological features of levodopa-responsive parkinsonism in multiple system atrophy: an autopsy case report and comparative neuropathological study |
| title_full_unstemmed | Neuropathological features of levodopa-responsive parkinsonism in multiple system atrophy: an autopsy case report and comparative neuropathological study |
| title_short | Neuropathological features of levodopa-responsive parkinsonism in multiple system atrophy: an autopsy case report and comparative neuropathological study |
| title_sort | neuropathological features of levodopa responsive parkinsonism in multiple system atrophy an autopsy case report and comparative neuropathological study |
| topic | multiple system atrophy levodopa putamen pathology presynaptic dopaminergic fibers |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2023.1293732/full |
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