Correlation of striatal dopamine transporter imaging with post mortem substantia nigra cell counts

Kraemmer, Julia; Kovács, Gábor G.; Perju‐Dumbravă, Lăcrămioara; Pirker, Susanne; Traub-Weidinger, Tatjana; Pirker, Walter

doi:10.1002/mds.25975

Cited by 113 publications

(88 citation statements)

References 23 publications

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“…DAT receptors are located on the dendrites of the nerve cells projecting to the striatum from the substantia nigra. The lower DAT binding in the striatum may reflect the loss of dopaminergic neurons (Kraemmer et al, 2014), which results in the impairment of endogenous dopamine release. Therefore, our finding may suggest that the long-term effect of CO exposure might be evident in dopaminergic neurons but not in the DAT receptor, per se.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal changes in the dopamine transporter and cognition in suicide attempters with charcoal burning

Yang

Wang

Hsieh

et al. 2015

Psychiatry Research: Neuroimaging

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Section: Discussionmentioning

confidence: 99%

Longitudinal changes in the dopamine transporter and cognition in suicide attempters with charcoal burning

Yang

Wang

Hsieh

et al. 2015

Psychiatry Research: Neuroimaging

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“…Conversely, at the 22-month follow-up time point of the PRECEPT study [13], 3 out of 629 cases with an initial abnormal scan (0.5%) switched to a normal category, implying that the first scan was incorrectly assigned an abnormal label. However, in none of the studies mentioned above was the quality of the scan interpretation challenged or even discussed, yet the need for semi-quantitative values has been strongly suggested in recent publications [4,6], further supported by the finding of a direct correlation between dopamine transporter uptake and neuromelanin-positive nigral cell count on pathological specimens [25]. Technical issues (misalignment of scan, medication interfering with dopaminergic uptake of SPECT) can also play a role.…”

Section: Discussionmentioning

confidence: 99%

Scan without evidence of dopaminergic deficit: A 10-year retrospective study

Nicastro

Garibotto

Badoud

et al. 2016

Parkinsonism & Related Disorders

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Introduction: 123 I-ioflupane SPECT is a powerful method to assess nigrostriatal dopamine system integrity. Several independent studies have shown that 1e15% of patients with suspected degenerative parkinsonism, mainly PD, have scans without evidence of dopaminergic deficit (SWEDD). It has been proposed that most SWEDD patients either present with a non-degenerative condition mimicking PD, such as atypical tremor or dystonia, or demonstrate an abnormal scan when repeated later. We here hypothesized that scan interpretation methods may also play a crucial yet underestimated role in this issue. Methods: We previously established age-dependent reference values of striatal uptake by analyzing scans from a cohort of patients with non-degenerative conditions. We then studied a large population with well-established degenerative parkinsonism (N ¼ 410, 80% with PD), using identical imaging protocol, to evaluate the prevalence of patients with normal scans based on routine visual assessment. Each scan was eventually reassessed using the same automated method as for controls and a detailed 3D analysis. Results: Ten potential SWEDD cases (2.4%) were identified. However, both reassessment methods independently showed that these scans were all outside reference limits and/or visually abnormal when reexamined carefully, except for one case (0.2%) with corticobasal syndrome. Conclusion: SPECT misinterpretation emerges as an important contributor to the SWEDD population, suggesting that suspected SWEDD cases should prompt not only a serious diagnosis challenge but, equally important, a detailed scan reassessment. True SWEDD cases seem extremely rare in degenerative parkinsonism. We propose that the very concept of SWEDD is more confusing than helpful and should be definitely abandoned.

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“…Previous molecular imaging studies have showed that PD is associated with substantial loss of striatal dopamine function (3,10). The degree of dopaminergic damage is the most pronounced in the posterior parts of the striatum but also occurs in the anterior striatum and other brain regions (3).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have provided uniform evidence that there is reduction in the striatal 123 I-FP-CIT signal, which correlates with the severity of the nigrostriatal cell loss in PD (10). In the clinical practice, 123 I-FP-CIT is used as a dopamine transporter (DAT) ligand, but it binds to other monoamine transporters as well.…”

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confidence: 99%

Dorsal-to-Ventral Shift in Midbrain Dopaminergic Projections and Increased Thalamic/Raphe Serotonergic Function in Early Parkinson Disease

et al. 2015

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Loss of nigrostriatal neurons leading to dopamine depletion in the dorsal striatum is the pathologic hallmark of Parkinson disease contributing to the primary motor symptoms of the disease. However, Parkinson pathology is more widespread in the brain, affecting also other dopaminergic pathways and neurotransmitter systems, but these changes are less well characterized. This study aimed to investigate the mesencephalic striatal and extrastriatal dopaminergic projections together with extrastriatal serotonin transporter binding in Parkinson disease. Methods: Two hundred sixteen patients with Parkinson disease and 204 control patients (patients without neurodegenerative parkinsonism syndromes and normal SPECT imaging) were investigated with SPECT using the dopamine/ serotonin transporter ligand 123 I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ( 123 I-FP-CIT) in the clinical setting. The group differences and midbrain correlations were analyzed voxel by voxel over the entire brain. Results: We found that Parkinson patients had lower 123 I-FP-CIT uptake in the striatum and ventral midbrain but higher uptake in the thalamus and raphe nuclei than control patients. In patients with Parkinson disease, the correlation of the midbrain tracer uptake was shifted from the putamen to widespread corticolimbic areas. All findings were highly significant at the voxel level familywise error-corrected P value of less than 0.05. Conclusion: Our findings show that Parkinson disease is associated not only with the degeneration of the nigrostriatal dopamine neurotransmission, but also with a parallel shift toward mesolimbic and mesocortical function. Furthermore, Parkinson disease patients seem to have upregulation of brain serotonin transporter function at the early phase of the disease.Key Words: dopamine; serotonin; SPECT; midbrain; raphe nuclei J Nucl Med 2015; 56:1036 56: -1041 56: DOI: 10.2967 Par kinson disease (PD) is a neurodegenerative condition characterized by the progressive accumulation of Lewy body inclusions beginning from the medulla and olfactory nuclei and gradually spreading through the midbrain to the neocortex (1). In the human brain, there are 2 major dopamine systems. The nigrostriatal pathway originates from the substantia nigra (SN) pars compacta (region A9) projecting to the putamen, and the ventral dopamine pathways (mesolimbic and mesocortical pathways) originate from the ventral tegmental area (VTA, A10) and innervate the limbic system and neocortex. PD pathology shows regional selectivity within the SN affecting the most ventrolateral-tier neurons that mainly project to the dorsal putamen (2), and molecular in vivo imaging studies have shown corresponding posterior-to-anterior gradient in the degeneration of the dopamine function within the striatum (3). However, to the best of our knowledge, no prior studies have investigated the midbrain projections within the dopamine system in PD.PD is primarily treated with medications that enhance the brain dopamine function, but not all symptoms...

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Correlation of striatal dopamine transporter imaging with post mortem substantia nigra cell counts

Cited by 113 publications

References 23 publications

Longitudinal changes in the dopamine transporter and cognition in suicide attempters with charcoal burning

Longitudinal changes in the dopamine transporter and cognition in suicide attempters with charcoal burning

Scan without evidence of dopaminergic deficit: A 10-year retrospective study

Dorsal-to-Ventral Shift in Midbrain Dopaminergic Projections and Increased Thalamic/Raphe Serotonergic Function in Early Parkinson Disease

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