Journal of Movement Disorders

Case Report

Nearly Abolished Dopamine Transporter Uptake in a Patient With a Novel FBXO7 Mutation: Eun Young Kim, Seon Young Kim, Youngduk Seo, Chaewon Shin; J Mov Disord. 2022;15(3):269-272. Published online July 26, 2022; DOI: https://doi.org/10.14802/jmd.22006

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Mutations in the F-box only protein 7 (FBXO7) gene are the cause of autosomal recessive parkinsonian-pyramidal syndrome. Herein, we report a patient with a novel FBXO7 mutation with a unique clinical presentation. A 43-year-old male visited our hospital with complaints of progressing gait disturbance since a generalized tonic clonic seizure. There were no past neurological symptoms or familial disorders. Neurological examination revealed bradykinesia, masked face, stooped posture, parkinsonian gait, and postural instability. The bilateral uptake by dopamine transporters was nearly abolished, as determined by N-(3-[18F]fluoropropyl)- 2β-carbon ethoxy-3β-(4-iodophenyl) nortropane positron emission tomography (18F-FP-CIT PET). Next-generation sequencing revealed a heterozygous c.1066_1069delTCTG (p.Ser356ArgfsTer56) frameshift variant and a heterozygous c.80G>A (p.Arg27His) missense variant of the FBXO7 gene. The patient’s specific clinical features, medication-refractory parkinsonism and seizures further broaden the spectrum of FBXO7 mutations. The nearly abolished dopamine transporter uptake identified by 18F-FP-CIT PET is frequently found in patients with FBXO7 mutations, which is different from the usual rostrocaudal gradient that is observed in patients with Parkinson’s disease.

Citations

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Imaging Procedure and Clinical Studies of [18F]FP-CIT PET
Changhwan Sung, Seung Jun Oh, Jae Seung Kim
Nuclear Medicine and Molecular Imaging.2024; 58(4): 185. CrossRef
Study of an FBXO7 patient mutation reveals Fbxo7 and PI31 co‐regulate proteasomes and mitochondria
Sara Al Rawi, Lorna Simpson, Guðrún Agnarsdóttir, Neil Q. McDonald, Veronika Chernuha, Orly Elpeleg, Massimo Zeviani, Roger A. Barker, Ronen Spiegel, Heike Laman
The FEBS Journal.2024; 291(12): 2565. CrossRef
The characteristics of FBXO7 and its role in human diseases
Yeling Zhong, Jinyun Li, Meng Ye, Xiaofeng Jin
Gene.2023; 851: 146972. CrossRef

Review Article

Emerging Concepts of Motor Reserve in Parkinson’s Disease: Seok Jong Chung, Jae Jung Lee, Phil Hyu Lee, Young H. Sohn; J Mov Disord. 2020;13(3):171-184. Published online August 31, 2020; DOI: https://doi.org/10.14802/jmd.20029

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Abstract PDF

The concept of cognitive reserve (CR) in Alzheimer’s disease (AD) explains the differences between individuals in their susceptibility to AD-related pathologies. An enhanced CR may lead to less cognitive deficits despite severe pathological lesions. Parkinson’s disease (PD) is also a common neurodegenerative disease and is mainly characterized by motor dysfunction related to striatal dopaminergic depletion. The degree of motor deficits in PD is closely correlated to the degree of dopamine depletion; however, significant individual variations still exist. Therefore, we hypothesized that the presence of motor reserve (MR) in PD explains the individual differences in motor deficits despite similar levels of striatal dopamine depletion. Since 2015, we have performed a series of studies investigating MR in de novo patients with PD using the data of initial clinical presentation and dopamine transporter PET scan. In this review, we summarized the results of these published studies. In particular, some premorbid experiences (i.e., physical activity and education) and modifiable factors (i.e., body mass index and white matter hyperintensity on brain image studies) could modulate an individual’s capacity to tolerate PD pathology, which can be maintained throughout disease progression.

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Original Articles

Heterogeneous Patterns of Striatal Dopamine Loss in Patients with Young- versus Old-Onset Parkinson’s Disease: Impact on Clinical Features: Seok Jong Chung, Han Soo Yoo, Yang Hyun Lee, Phil Hyu Lee, Young H. Sohn; J Mov Disord. 2019;12(2):113-119. Published online May 30, 2019; DOI: https://doi.org/10.14802/jmd.18064

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163 Download
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28 Crossref

Abstract PDF Supplementary Material

Objective
Ample evidence has suggested that age at onset of Parkinson’s disease (PD) is associated with heterogeneous clinical features in individuals. We hypothesized that this may be attributed to different patterns of nigrostriatal dopamine loss.
Methods
A total of 205 consecutive patients with de novo PD who underwent 18F-FP-CIT PET scans (mean follow-up duration, 6.31 years) were divided into three tertile groups according to their age at onset of parkinsonian motor symptoms. Striatal dopamine transporter (DAT) availability was compared between the old- (n = 73) and young-onset (n = 66) groups. In addition, the risk of developing freezing of gait (FOG) and longitudinal requirements for dopaminergic medications were examined.
Results
The old-onset PD group (mean age at onset, 72.66 years) exhibited more severe parkinsonian motor signs than the young-onset group (52.58 years), despite comparable DAT availability in the posterior putamen; moreover, the old-onset group exhibited more severely decreased DAT availability in the caudate than the young-onset group. A Cox regression model revealed that the old-onset PD group had a higher risk for developing FOG than the young-onset group [hazard ratio 2.523, 95% confidence interval (1.239–5.140)]. The old-onset group required higher doses of dopaminergic medications for symptom control than the young-onset group over time.
Conclusion
The present study demonstrated that the old-onset PD group exhibited more severe dopamine loss in the caudate and were more likely to develop gait freezing, suggesting that age at onset may be one of the major determinants of the pattern of striatal dopamine depletion and progression of gait disturbance in PD.

Citations

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The Molecular Pathway of p75 Neurotrophin Receptor (p75NTR) in Parkinson’s Disease: The Way of New Inroads
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Molecular Neurobiology.2024; 61(5): 2469. CrossRef
Patterns of regional cerebral hypoperfusion in early Parkinson's disease: Clinical implications
Seok Jong Chung, Su Hong Kim, Chan Wook Park, Hye Sun Lee, Mijin Yun, Yun Joong Kim, Young H. Sohn, Yong Jeong, Phil Hyu Lee
Parkinsonism & Related Disorders.2024; 121: 106024. CrossRef
Therapeutic Potential Effect of Glycogen Synthase Kinase 3 Beta (GSK-3β) Inhibitors in Parkinson Disease: Exploring an Overlooked Avenue
Areej Turkistani, Hayder M. Al-kuraishy, Ali I. Al-Gareeb, Ali K. Albuhadily, Athanasios Alexiou, Marios Papadakis, Mohamed M. Elfiky, Hebatallah M. Saad, Gaber El-Saber Batiha
Molecular Neurobiology.2024;[Epub] CrossRef
Imaging Procedure and Clinical Studies of [18F]FP-CIT PET
Changhwan Sung, Seung Jun Oh, Jae Seung Kim
Nuclear Medicine and Molecular Imaging.2024; 58(4): 185. CrossRef
Association of Family History and Polygenic Risk Score With Longitudinal Prognosis in Parkinson Disease
Mincheol Park, Young-gun Lee
Neurology Genetics.2024;[Epub] CrossRef
Hippocampal Perfusion Affects Motor and Cognitive Functions in Parkinson Disease: An Early Phase 18F‐FP‐CIT Positron Emission Tomography Study
Min Young Chun, Seok Jong Chung, Su Hong Kim, Chan Wook Park, Seong Ho Jeong, Hye Sun Lee, Phil Hyu Lee, Young H. Sohn, Yong Jeong, Yun Joong Kim
Annals of Neurology.2024; 95(2): 388. CrossRef
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Hayder M. Al-kuraishy, Esraa H. Fahad, Salah Al-Windy, Suzy A. El-Sherbeni, Walaa A. Negm, Gaber El-Saber Batiha
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Naif H. Ali, Hayder M. Al‐Kuraishy, Ali I. Al‐Gareeb, Athanasios Alexiou, Marios Papadakis, Ali Abdullah AlAseeri, Mubarak Alruwaili, Hebatallah M. Saad, Gaber El‐Saber Batiha
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Mid- and late-life lifestyle activities as main drivers of general and domain-specific cognitive reserve in individuals with Parkinson’s disease: cross-sectional and longitudinal evidence from the LANDSCAPE study
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Talia Herman, Yael Barer, Michal Bitan, Shani Sobol, Nir Giladi, Jeffrey M. Hausdorff
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Yae Ji Kim, Chan Wook Park, Hye Won Shin, Hye Sun Lee, Yun Joong Kim, Mijin Yun, Phil Hyu Lee, Young H. Sohn, Yong Jeong, Seok Jong Chung
Parkinsonism & Related Disorders.2022; 102: 108. CrossRef
Potential Link Between Cognition and Motor Reserve in Patients With Parkinson’s Disease
Seok Jong Chung, Yae Ji Kim, Yun Joong Kim, Hye Sun Lee, Mijin Yun, Phil Hyu Lee, Yong Jeong, Young H. Sohn
Journal of Movement Disorders.2022; 15(3): 249. CrossRef
Association Between White Matter Networks and the Pattern of Striatal Dopamine Depletion in Patients With Parkinson Disease
Seok Jong Chung, Yae Ji Kim, Yun Joong Kim, Hye Sun Lee, Seong Ho Jeong, Ji-Man Hong, Young H. Sohn, Mijin Yun, Yong Jeong, Phil Hyu Lee
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Seok Jong Chung, John Hoon Rim, Dajeong Ji, Sangwon Lee, Han Soo Yoo, Jin Ho Jung, KyoungWon Baik, Yonghoon Choi, Byoung Seok Ye, Young H. Sohn, Mijin Yun, Sang-Guk Lee, Phil Hyu Lee
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Seok Jong Chung, Yun Joong Kim, Han Soo Yoo, Jin Ho Jung, KyoungWon Baik, Hye Sun Lee, Yang Hyun Lee, Ji-Man Hong, Young H Sohn, Phil Hyu Lee, Jay Magaziner
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Giovanni Palermo, Sara Giannoni, Daniela Frosini, Riccardo Morganti, Duccio Volterrani, Ubaldo Bonuccelli, Nicola Pavese, Roberto Ceravolo
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Xiaohong Li, Qizhou Zhang, Yongde Qin, Yubin Li, Nazimuguli Mutaerbieke, Xiaojia Zhao, Amina Yibulayin
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DaTSCAN (123I-FP-CIT SPECT) imaging in early versus mid and late onset Parkinson's disease: Longitudinal data from the PPMI study
Christos Koros, Athina-Maria Simitsi, Andreas Prentakis, Nikolaos Papagiannakis, Anastasia Bougea, Ioanna Pachi, Dimitra Papadimitriou, Ion Beratis, Sokratis G. Papageorgiou, Maria Stamelou, Xenia Geronicola Trapali, Leonidas Stefanis
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Nonmotor and Dopamine Transporter Change in REM Sleep Behavior Disorder by Olfactory Impairment: Jee-Young Lee, Eun Jin Yoon, Yu Kyeong Kim, Chae Won Shin, Hyunwoo Nam, Jae Min Jeong, Han-Joon Kim, Beomseok Jeon; J Mov Disord. 2019;12(2):103-112. Published online May 30, 2019; DOI: https://doi.org/10.14802/jmd.18061

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208 Download
19 Web of Science
17 Crossref

Abstract PDF Supplementary Material

Objective
It is unclear whether the decline in dopamine transporters (DAT) differs among idiopathic rapid eye movement sleep behavior disorder (iRBD) patients with different levels of olfactory impairment. This study aimed to characterize DAT changes in relation to nonmotor features in iRBD patients by olfactory loss.
Methods
This prospective cohort study consisted of three age-matched groups: 30 polysomnography-confirmed iRBD patients, 30 drug-naïve Parkinson’s disease patients, and 19 healthy controls without olfactory impairment. The iRBD group was divided into two groups based on olfactory testing results. Participants were evaluated for reported prodromal markers and then underwent 18F-FP-CIT positron emission tomography and 3T MRI. Tracer uptakes were analyzed in the caudate, anterior and posterior putamen, substantia nigra, and raphe nuclei.
Results
Olfactory impairment was defined in 38.5% of iRBD patients. Mild parkinsonian signs and cognitive functions were not different between the two iRBD subgroups; however, additional prodromal features, constipation, and urinary and sexual dysfunctions were found in iRBD patients with olfactory impairment but not in those without. Tracer uptake showed significant group differences in all brain regions, except the raphe nuclei. The iRBD patients with olfactory impairment had uptake reductions in the anterior and posterior putamen, caudate, and substantia nigra (p < 0.016 in all, adjusted for age), which ranged from 0.6 to 0.8 of age-normative values. In contrast, those without olfactory impairment had insignificant changes in all regions ranging above 0.8.
Conclusion
There was a clear distinction in DAT loss and nonmotor profiles by olfactory status in iRBD.

Citations

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Clinical Features Indicating Nigrostriatal Dopaminergic Degeneration in Drug-Induced Parkinsonism: Seung Ha Lee, Han Kyeol Kim, Young Gun Lee, Chul Hyoung Lyoo, Sung Jun Ahn, Myung Sik Lee; J Mov Disord. 2017;10(1):35-39. Published online December 27, 2016; DOI: https://doi.org/10.14802/jmd.16045

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Abstract PDF Supplementary Material

Objective
Patients with drug-induced parkinsonism (DIP) may have nigrostriatal dopaminergic degeneration. We studied the clinical features that may indicate nigrostriatal dopaminergic degeneration in patients with DIP.
Methods
Forty-one DIP patients were classified into normal and abnormal [¹⁸F] FP-CIT scan groups. Differences in 32 clinical features and drug withdrawal effects were studied.
Results
Twenty-eight patients had normal (Group I) and 13 patients had abnormal (Group II) scans. Eight patients of Group I, but none of Group II, had taken calcium channel blockers (p = 0.040). Three patients of Group I and six of Group II had hyposmia (p = 0.018). After drug withdrawal, Group I showed greater improvement in Unified Parkinson’s Disease Rating Scale total motor scores and subscores for bradykinesia and tremors than Group II. Only hyposmia was an independent factor associated with abnormal scans, but it had suboptimal sensitivity.
Conclusion
None of the clinical features were practical indicators of nigrostriatal dopaminergic degeneration in patients with DIP.

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Comparative Olfactory Profiles in Parkinson’s Disease and Drug-Induced Parkinsonism
In Hee Kwak, Young Eun Kim, Suk Yun Kang, Joong Seob Lee, Jeongjae Lee, Min Seung Kim, Dong A Yea, Hyeo-il Ma
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Retinal Thickness and Its Interocular Asymmetry Between Parkinson’s Disease and Drug-Induced Parkinsonism
Wool Suh, Sung Uk Baek, Jungsu S. Oh, Seung Yeon Seo, Jae Seung Kim, You Mie Han, Min Seung Kim, Suk Yun Kang
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Gait abnormalities and non-motor symptoms predict abnormal dopaminergic imaging in presumed drug-induced Parkinsonism
Whitley W. Aamodt, Jacob G. Dubroff, Gang Cheng, Betty Taylor, Stephanie Wood, John E. Duda, James F. Morley
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Gender Differences in Age-Related Striatal Dopamine Depletion in Parkinson’s Disease: Jae Jung Lee, Jee Hyun Ham, Phil Hyu Lee, Young H. Sohn; J Mov Disord. 2015;8(3):130-135. Published online September 10, 2015; DOI: https://doi.org/10.14802/jmd.15031

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Abstract PDF Supplementary Material

Objective Gender differences are a well-known clinical characteristic of Parkinson’s disease (PD). In-vivo imaging studies demonstrated that women have greater striatal dopamine transporter (DAT) activity than do men, both in the normal population and in PD patients. We hypothesize that women exhibit more rapid aging-related striatal DAT reduction than do men, as the potential neuroprotective effect of estrogen wanes with age.
Methods This study included 307 de novo PD patients (152 men and 155 women) who underwent DAT scans for an initial diagnostic work-up. Gender differences in age-related DAT decline were assessed in striatal sub-regions using linear regression analysis.
Results Female patients exhibited greater DAT activity compared with male patients in all striatal sub-regions. The linear regression analysis revealed that age-related DAT decline was greater in the anterior and posterior caudate, and the anterior putamen in women compared with men; we did not observe this difference in other sub-regions.
Conclusions This study demonstrated the presence of gender differences in age-related DAT decline in striatal sub-regions, particularly in the antero-dorsal striatum, in patients with PD, presumably due to aging-related decrease in estrogen. Because this difference was not observed in the sensorimotor striatum, this finding also suggests that women may not have a greater capacity to tolerate PD pathogenesis than do men.

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