Neuromelanin in parkinsonian disorders: an update

Martín-Bastida, Antonio; Pietracupa, Sara; Piccini, Paola

doi:10.1080/00207454.2017.1325883

Cited by 34 publications

(27 citation statements)

References 45 publications

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“…Neurochemical content and receptor expression are also very heterogeneous containing adrenergic, GABAergic, serotonergic, glutamatergic, µ-opioid, orexin/hypocreatin, nicotinic acetylcholine, and cannabinoid receptors (reviewed in Berridge and Waterhouse, 2003;Schwarz and Luo, 2015). LC noradrenergic cells, as happens with SNc neurons, also contains neuromelanin which makes them specially vulnerable to neurodegeneration in PD (reviewed in Martin-Bastida et al, 2017 andVila, 2019).…”

Section: The Locus Coeruleusmentioning

confidence: 99%

The Noradrenergic System in Parkinson’s Disease

et al. 2020

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Nowadays it is well accepted that in Parkinson's disease (PD), the neurodegenerative process occurs in stages and that damage to other areas precedes the neuronal loss in the substantia nigra pars compacta, which is considered a pathophysiological hallmark of PD. This heterogeneous and progressive neurodegeneration may explain the diverse symptomatology of the disease, including motor and non-motor alterations. In PD, one of the first areas undergoing degeneration is the locus coeruleus (LC). This noradrenergic nucleus provides extensive innervation throughout the brain and plays a fundamental neuromodulator role, participating in stress responses, emotional memory, and control of motor, sensory, and autonomic functions. Early in the disease, LC neurons suffer modifications that can condition the effectiveness of pharmacological treatments, and importantly, can lead to the appearance of common non-motor symptomatology. The noradrenergic system also exerts anti-inflammatory and neuroprotective effect on the dopaminergic degeneration and noradrenergic damage can consequently condition the progress of the disease. From the pharmacological point of view, it is also important to understand how the noradrenergic system performs in PD, since noradrenergic medication is often used in these patients, and drug interactions can take place when combining them with the gold standard drug therapy in PD, L-3,4-dihydroxyphenylalanine (L-DOPA). This review provides an overview about the functional status of the noradrenergic system in PD and its contribution to the efficacy of pharmacologicalbased treatments. Based on preclinical and clinical publications, a special attention will be dedicated to the most prevalent non-motor symptoms of the disease.

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Section: The Locus Coeruleusmentioning

confidence: 99%

The Noradrenergic System in Parkinson’s Disease

et al. 2020

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“…As in PD, PSP patients also show a reduction in the neuromelanin signal and volume of the SNpc (27,81,82) and a loss of the DNH sign (37). Neuropathological studies have reported a different pattern of nigral degeneration from PD without predilection for the lateral part (7).…”

Section: Conventional and Structural Imaging Substantia Nigramentioning

confidence: 99%

The Role of Magnetic Resonance Imaging for the Diagnosis of Atypical Parkinsonism

et al. 2020

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The diagnosis of Parkinson's disease and atypical Parkinsonism remains clinically difficult, especially at the early stage of the disease, since there is a significant overlap of symptoms. Multimodal MRI has significantly improved diagnostic accuracy and understanding of the pathophysiology of Parkinsonian disorders. Structural and quantitative MRI sequences provide biomarkers sensitive to different tissue properties that detect abnormalities specific to each disease and contribute to the diagnosis. Machine learning techniques using these MRI biomarkers can effectively differentiate atypical Parkinsonian syndromes. Such approaches could be implemented in a clinical environment and improve the management of Parkinsonian patients. This review presents different structural and quantitative MRI techniques, their contribution to the differential diagnosis of atypical Parkinsonian disorders and their interest for individual-level diagnosis.

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“…Another T 2 *-related marker is the so-called "swallow tail sign" on susceptibility weighted imaging in parkinsonism [8,9]. MRI with neuromelanin sensitive T 1 -weighted sequences has been shown to exhibit changes in PD and atypical parkinsonism, with reduced neuromelanin signal volumes in the substantia nigra in PD, PSP, MSA and corticobasal degeneration compared to healthy controls [10,11]. However, these methods require specialized protocols, relatively complicated post-processing or manual ratings as part of their application, making them not as readily available as structural MRI measurements.…”

Section: Introductionmentioning

confidence: 99%

Automated brainstem volumetry can aid in the diagnostics of parkinsonian disorders

Sjöström

Granberg

Hashim

et al. 2020

Parkinsonism & Related Disorders

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Separating progressive supranuclear palsy (PSP) from Parkinson's disease (PD) and multiple system atrophy (MSA) is often challenging in early disease but is important for appropriate management. Magnetic resonance imaging (MRI) can aid the diagnostics and manual 2D measurements are often used. However, new fully automatic brainstem volumetry could potentially be more accurate and increase availability of brainstem metrics. Methods: Clinical 3D T1-weighted MRI were obtained from 196 consecutive patients; 29 PSP, 27 MSA, 140 PD. Midbrain-pons ratio and magnetic resonance parkinsonism index (MRPI) 1.0 and 2.0 were manually calculated, and intra-rater and inter-rater reliability was assessed. FreeSurfer was used to automatically segment brainstem substructures, normalized to the intracranial volume. The robustness of the automated analysis was evaluated in 3 healthy controls. The diagnostic accuracy of the brainstem biomarkers was assessed using receiver operating characteristic curves. Results: Automatic brainstem volumetry had good repeatability/reproducibility with intra-scanner coefficient of variation 0.3-5.5% and inter-scanner coefficient of variation 0.9-8.4% in the different brainstem regions. Midbrain volume performs better than planimetric measurements in separating PSP from PD (Area under the curve (AUC) 0.90 compared with 0.81 for midbrain-pons ratio (p = 0.019), 0.77 for MRPI 1.0 (p = 0.007) and 0.81 for MRPI 2.0 (p = 0.021)). Midbrain volume performed on par with planimetry for separation between PSP and MSA. Conclusion: Automatic brainstem segmentation is robust and shows promising diagnostic performance in separating PSP from PD and MSA. If further developed, it could play a role in diagnosing PSP and could potentially be used as an outcome in clinical trials.

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Neuromelanin in parkinsonian disorders: an update

Cited by 34 publications

References 45 publications

The Noradrenergic System in Parkinson’s Disease

The Noradrenergic System in Parkinson’s Disease

The Role of Magnetic Resonance Imaging for the Diagnosis of Atypical Parkinsonism

Automated brainstem volumetry can aid in the diagnostics of parkinsonian disorders

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