Nigral Iron Deposition Is Associated With Levodopa-Induced Dyskinesia in Parkinson’s Disease

Song, Tianbin; Li, Jiping; Mei, Shanshan; Jia, Xiaofei; Yang, H. K.; Ye, Yongquan; Yuan, Jian‐Min; Zhang, Yuqing; Lu, Jie

doi:10.3389/fnins.2021.647168

Cited by 8 publications

(11 citation statements)

References 44 publications

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“…Our retrospective study indicated that early and regular treatment with levodopa prevented the loss of DNH and alleviated the symptoms of PD. A recent study suggested that the nigral iron deposition was associated with levodopa-induced dyskinesia ( Song et al, 2021 ). However, in our study, decreased loss of DNH was observed in one patient with more severe dyskinesia.…”

Section: Discussionmentioning

confidence: 99%

Modified Iron Deposition in Nigrosomes by Pharmacotherapy for the Management of Parkinson’s Disease

Wang

et al. 2022

Front. Mol. Biosci.

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Background: Increased iron deposition in nigrosome as assessed by susceptibility-weighted imaging (SWI) is involved in the pathogenesis of Parkinson’s disease (PD). This study investigated the effects of antiparkinson drugs on iron deposition in the nigrosome of PD patients.Methods: Based on the retrospective analysis of clinical data, alterations in iron deposition in the substantia nigra were investigated in 51 PD patients across different types of therapies and in nine Parkinson-plus syndrome patients. The Movement Disorder Society revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part Ⅲ/Ⅳ (UPDRS Ⅲ/Ⅳ) was utilized to evaluate motor function and complications. SWI (slice = 0.6 mm) was used to detect iron deposition in the nigrosome and substantia nigra. Nigrosome loss was scored on a 1-point nigrosome visibility scale. Visual assessment of dorsolateral nigral hyperintensity (DNH) was separately performed for each side of the nigrosome with SWI.Results: Increased UPDRS Ⅲ scores were correlated with low nigrosome scores based on correlation analysis at a disease duration of 6–12 months (r = −0.8420). The loss of the nigrosome on SWI was clearly inhibited in PD patients with a 3–5-year duration of administration of antiparkinson medications compared with no treatment. Decreased UPDRS Ⅲ scores and increased nigrosome scores were observed in the regular treatment of PD patients with a 6–7-year disease duration. For patients with Parkinson-plus syndromes, such as multiple system atrophy, iron accumulation was apparent in the corpus striatum and substantia nigra compared with that for patients with progressive supranuclear palsy.Conclusions: Early and regular treatment with antiparkinson drugs not only alleviates the chance of PD disability but also prevents the loss of DNH, namely, iron accumulation in the nigrosome.

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Section: Discussionmentioning

confidence: 99%

Modified Iron Deposition in Nigrosomes by Pharmacotherapy for the Management of Parkinson’s Disease

Wang

et al. 2022

Front. Mol. Biosci.

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“…35 Nigral cell degeneration leads to the functional alterations of basal ganglia, which are related to motor dysfunction in patients with PD. 11,36 On the other side, some studies suggested that iron accumulation might also result from dopaminergic cell degeneration. 37,38 NM is a pigment and is particularly abundant in dopamine neurons of the SN and in the noradrenergic neurons of locus coeruleus.…”

Section: Discussionmentioning

confidence: 99%

“…A study using quantitative susceptibility mapping (QSM) imaging showed that the QSM values of SN in PD-LID were higher than in PD without LID (PD-nLID), suggesting that dyskinesia is related to excessive iron deposition in SN. 11 However, current studies in LID mainly focus on the entire SN; the dopaminergic changes in the subregions of SN have not been investigated. The substantia nigra pars compacta (SNpc) is composed of closely packed dopaminergic neurons, 12 which may contribute to the abnormal dopaminergic responses that result in LID.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, advanced neuroimaging techniques have provided opportunities to characterize the structural and functional alterations of the SN associated with patients with PD‐LID. A study using quantitative susceptibility mapping (QSM) imaging showed that the QSM values of SN in PD‐LID were higher than in PD without LID (PD‐nLID), suggesting that dyskinesia is related to excessive iron deposition in SN 11 . However, current studies in LID mainly focus on the entire SN; the dopaminergic changes in the subregions of SN have not been investigated.…”

Section: Introductionmentioning

confidence: 99%

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Multimodal Imaging of Substantia Nigra in Parkinson's Disease with Levodopa‐Induced Dyskinesia

Gan

Zhang

et al. 2023

Movement Disorders

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A BS TRACT: Background: Degeneration of the substantia nigra (SN) may contribute to levodopainduced dyskinesia (LID) in Parkinson's disease (PD), but the exact characteristics of SN in LID remain unclear. Objective: To further understand the pathogenesis of patients with PD with LID (PD-LID), we explored the structural and functional characteristics of SN in PD-LID using multimodal magnetic resonance imaging (MRI). Methods: Twenty-nine patients with PD-LID, 37 patients with PD without LID (PD-nLID), and 28 healthy control subjects underwent T1-weighted MRI, quantitative susceptibility mapping, neuromelanin-sensitive MRI, multishell diffusion MRI, and resting-state functional MRI. Different measures characterizing the SN were obtained using a region of interest-based approach. Results: Compared with patients with PD-nLID and healthy control subjects, the quantitative susceptibility mapping values of SN pars compacta (SNpc) were significantly higher (P = 0.049 and P = 0.00002), and the neuromelanin contrast-to-noise ratio values in SNpc were significantly lower (P = 0.012 and P = 0.000002) in PD-LID. The intracellular volume fraction of the posterior SN in PD-LID was significantly higher compared with PD-nLID (P = 0.037). Resting-state fMRI indicated that PD-LID in the medication off state showed higher functional connectivity between the SNpc and putamen compared with PD-nLID (P = 0.031), and the functional connectivity changes in PD-LID were positively correlated with Unified Dyskinesia Rating Scale total scores (R = 0.427, P = 0.042). Conclusions: Our multimodal imaging findings highlight greater neurodegeneration in SN and the altered nigrostriatal connectivity in PD-LID. These characteristics provide a new perspective into the role of SN in the pathophysiological mechanisms underlying PD-LID.

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“…Furthermore, the published studies did not always identify the same regions of interest and did not consider the medications that the patients were taking at the time the FDG-PET or QSM–MRI brain imaging studies were performed. For example, subjects with levodopa-induced dyskinesia have more iron in the substantia nigra than those without it [ 83 ]. It is also apparent that the results would be more accurate if studies were identified where FDG-PET and QSM–MRI were both conducted on the same patients or on age- and sex-matched pairs.…”

Section: Discussionmentioning

confidence: 99%

Brain Glucose Hypometabolism and Iron Accumulation in Different Brain Regions in Alzheimer’s and Parkinson’s Diseases

et al. 2022

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The aim of this study was to examine the relationship between the presence of glucose hypometabolism (GHM) and brain iron accumulation (BIA), two potential pathological mechanisms in neurodegenerative disease, in different regions of the brain in people with late-onset Alzheimer’s disease (AD) or Parkinson’s disease (PD). Studies that conducted fluorodeoxyglucose positron emission tomography (FDG-PET) to map GHM or quantitative susceptibility mapping—magnetic resonance imaging (QSM–MRI) to map BIA in the brains of patients with AD or PD were reviewed. Regions of the brain where GHM or BIA were reported in each disease were compared. In AD, both GHM and BIA were reported in the hippocampus, temporal, and parietal lobes. GHM alone was reported in the cingulate gyrus, precuneus and occipital lobe. BIA alone was reported in the caudate nucleus, putamen and globus pallidus. In PD, both GHM and BIA were reported in thalamus, globus pallidus, putamen, hippocampus, and temporal and frontal lobes. GHM alone was reported in cingulate gyrus, caudate nucleus, cerebellum, and parietal and occipital lobes. BIA alone was reported in the substantia nigra and red nucleus. GHM and BIA are observed independent of one another in various brain regions in both AD and PD. This suggests that GHM is not always necessary or sufficient to cause BIA and vice versa. Hypothesis-driven FDG-PET and QSM–MRI imaging studies, where both are conducted on individuals with AD or PD, are needed to confirm or disprove the observations presented here about the potential relationship or lack thereof between GHM and BIA in AD and PD.

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Nigral Iron Deposition Is Associated With Levodopa-Induced Dyskinesia in Parkinson’s Disease

Cited by 8 publications

References 44 publications

Modified Iron Deposition in Nigrosomes by Pharmacotherapy for the Management of Parkinson’s Disease

Modified Iron Deposition in Nigrosomes by Pharmacotherapy for the Management of Parkinson’s Disease

Multimodal Imaging of Substantia Nigra in Parkinson's Disease with Levodopa‐Induced Dyskinesia

Brain Glucose Hypometabolism and Iron Accumulation in Different Brain Regions in Alzheimer’s and Parkinson’s Diseases

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