Changes in substantia nigra and locus coeruleus in patients with early-stage Parkinson's disease using neuromelanin-sensitive MR imaging

This study proposed to detect changes in brain microstructure in patients with Parkinson’s disease (PD) using diffusion kurtosis imaging (DKI) to quantitatively diagnose early-stage PD. Conventional magnetic resonance imaging and DKI scanning were performed in 24 patients with PD and in 12 age- and sex-matched healthy participants. Hoehn and Yahr (H–Y) stage and Unified Parkinson’s Disease Rating Scale-III (UPDRS-III) scores were obtained from both groups. The mean kurtosis (MK), axial kurtosis, and radial kurtosis of the bilateral substantia nigra on DKI were measured and compared between the two groups. The correlations between MK, H–Y stage, and UPDRS-III scores were determined. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficacy of MK for PD in the substantia nigra. The MK value in the PD group was 0.971. The area under the ROC curve of the substantia nigra was 0.905; the sensitivity and specificity were 0.917 and 0.875, respectively, and the cutoff value was 1.046. The MK of the substantia nigra in the PD group had no significant correlation with the H–Y stages but was negatively correlated with the UPDRS-III scores ([Formula: see text]; [Formula: see text]). Our research identified DKI as a novel tool for the qualitative diagnosis of PD. The optimal MK value for PD diagnosis could be determined with ROC analysis.

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Lack of Association of Locus Coeruleus Pathology with Orthostatic Hypotension in Parkinson’s Disease

Journal of Parkinson s Disease ◽

10.3233/jpd-202325 ◽

2020 ◽

pp. 1-5

Author(s):

Qiang Tong ◽

Liam Chen

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Substantia Nigra ◽

Orthostatic Hypotension ◽

Locus Coeruleus ◽

The Elderly ◽

Motor Symptom ◽

Postmortem Brains ◽

The Relationship ◽

The Brain

Orthostatic hypotension (OH) is a common non-motor symptom in Parkinson’s disease (PD) and is linked with increased mortality risk among the elderly. Although the locus coeruleus (LC) is the major source of noradrenaline (NA) modulation in the brain, its role in the pathogenesis of OH in PD remains largely elusive. Here we examined 44 well characterized postmortem brains of PD patients and available clinical data to explore the relationship between OH and LC pathology in PD. Our results failed to indicate that the LC pathology as well as the substantia nigra pathology were robustly associated with the presence of OH in PD patients, suggesting targeting LC norepinephrinergic system alone may not be sufficient to treat OH in PD.

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AAV2/DJ-mediated alpha-synuclein overexpression in the rat substantia nigra as early stage model of Parkinson’s disease

Cell and Tissue Research ◽

10.1007/s00441-019-03013-x ◽

2019 ◽

Vol 378 (1) ◽

pp. 1-14

Author(s):

Friederike Freiin von Hövel ◽

Regina Rumpel ◽

Andreas Ratzka ◽

Dietmar Schreiner ◽

Claudia Grothe

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Substantia Nigra ◽

Early Stage ◽

Alpha Synuclein ◽

Stage Model ◽

Rat Substantia Nigra

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Striatal silent lacunar infarction is associated with changes to the substantia nigra in patients with early-stage Parkinson’s disease: A diffusion kurtosis imaging study

Journal of Clinical Neuroscience ◽

10.1016/j.jocn.2016.03.032 ◽

2016 ◽

Vol 33 ◽

pp. 138-141 ◽

Cited By ~ 7

Author(s):

Guohua Zhang ◽

Yuhu Zhang ◽

Chengguo Zhang ◽

Yukai Wang ◽

Guixian Ma ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Substantia Nigra ◽

Early Stage ◽

Imaging Study ◽

Lacunar Infarction ◽

Diffusion Kurtosis Imaging ◽

Diffusion Kurtosis

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Independent loss of melanin-containing neurons between the locus coeruleus and substantia nigra in Parkinson’s disease

Journal of the Neurological Sciences ◽

10.1016/j.jns.2017.08.2082 ◽

2017 ◽

Vol 381 ◽

pp. 738

Author(s):

K. Sugaya ◽

T. Inoue ◽

Y. Nakata ◽

E. Isozaki

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Substantia Nigra ◽

Locus Coeruleus

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Pronounced α-synuclein pathology in a seeding-based mouse model is not sufficient to induce mitochondrial respiration deficits in the striatum and amygdala

10.1101/2020.03.26.006189 ◽

2020 ◽

Author(s):

Johannes Burtscher ◽

Jean-Christophe Copin ◽

Carmen Sandi ◽

Hilal A. Lashuel

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Substantia Nigra ◽

Mitochondrial Dysfunction ◽

Mitochondrial Respiration ◽

Early Stage ◽

Relevant Literature ◽

Brain Regions ◽

Substantia Nigra Pars Compacta ◽

Ros Generation

AbstractIncreasing evidence suggests that crosstalk between α-synuclein pathology formation and mitochondrial dysfunctions plays a central role in the pathogenesis of Parkinson’s disease and related synucleinopathies. While mitochondrial dysfunction is a well-studied phenomenon in the substantia nigra, which is selectively vulnerable in Parkinson’s disease and some models thereof, less information is available in other brain regions that are also affected by synuclein pathology.Therefore, we sought to test the hypothesis that early α-synuclein pathology causes mitochondrial dysfunction, and that this effect might be exacerbated in conditions of increased vulnerability of affected brain regions, such as the amygdala.We combined a model of intracerebral α-synuclein pathology seeding with chronic glucocorticoid treatment modelling non-motor symptoms of Parkinson’s disease and affecting amygdala physiology. We measured mitochondrial respiration, ROS generation and protein abundance as well as α-synuclein pathology in male mice.Chronic corticosterone administration induced mitochondrial hyperactivity in the amygdala. Although injection of α-synuclein preformed fibrils into the striatum resulted in pronounced α-synuclein pathology in both striatum and amygdala, mitochondrial respiration in these brain regions was altered in neither chronic corticosterone nor control conditions.Our results suggest that early stage α-synuclein pathology does not influence mitochondrial respiration in the striatum and amygdala, even in corticosterone-induced respirational hyperactivity. We discuss our findings in light of relevant literature, warn of a potential publication bias and encourage scientist to report their negative results in the frame of this model.Significance statementWe provide evidence that early stage synucleinopathy by itself or in combination with exogenous corticosterone induced amygdala hyperactivity did not compromise mitochondrial respiration in the striatum and amygdala in one of the most commonly used models of synucleinopathies. These results may explain, why this model in the hands of many research groups does not elicit pronounced Parkinson’s disease like symptoms in the absence of mitochondrial dysfunction in brain regions strongly affected by synuclein pathology and involved in non-motor (amygdala) and motor (striatum) symptoms. Our findings call for rigorous investigation of the short- and long-term effects of α-synuclein pathology on mitochondrial function/dysfunction in this model, in particular in brain regions strongly affected by neurodegeneration such as the substantia nigra pars compacta.

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Unilateral loss of the swallow tail sign in a patient with idiopathic Parkinson’s disease

Journal Of Cardiovascular, Neurovascular & Stroke ◽

10.32896/cvns.v3n3.59-62 ◽

2021 ◽

Vol 3 (3) ◽

pp. 59-62

Author(s):

Anna Misyail Abd Rashid ◽

Mohamad Syafeeq Faeez Md Noh ◽

Abdul Hanif Khan Yusof Khan ◽

Mohd Naim Mohd Yaakob ◽

Norafida Bahari ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Substantia Nigra ◽

Predictive Value ◽

Early Stage ◽

Imaging Biomarker ◽

Idiopathic Parkinson’S Disease ◽

Yahr Stage ◽

Hand Tremor ◽

Idiopathic Parkinson's Disease

A 66-year-old man with underlying hypertension and dyslipidemia presented with left hand tremor for one year. He also noticed difficulty in initiating movement and slowness in activities of daily living. On examination, he was noted to have mask-like facies with reduced blinking and monotonous speech. There was presence of resting pill-rolling tremor, bradykinesia, and cogwheel rigidity which was worst on the left upper limb. Gait assessment revealed difficulty in standing up, shuffling gait with reduced arm swing which was more prominent on the left side, and turning in numbers. No cerebellar signs and supranuclear palsy were present to suggest Parkinson-plus syndrome. Susceptibility weighted imaging (SWI) showed loss of the swallow tail sign on the right side [Figure 1]. The clinical presentation, supplemented by the imaging findings were concluded to be pathognomonic of idiopathic Parkinson’s disease (IPD), Hoehn & Yahr stage 1. He was started on levodopa and benserazide twice daily with improvement of symptoms.The nigrosomes are primary subregions of the substantia nigra where dopaminergic cells are lost in IPD. Within these nigrosomes, maximal cell loss occurs in nigrosome-1; the largest subgroup of nigrosomes. Normally, they appear as a SWI-hyperintense area surrounded by hypointensity within the dorsolateral substantia nigra, akin to a swallow’s tail. In one study, poor visualization of nigrosome-1 was significantly associated with higher motor asymmetry in the contralateral side (sensitivity 98.5%, specificity 93.6%, positive-predictive value 98.3%, negative-predictive value 98.3% and an accuracy of 96%) [1]. Noh et al [2] showed that abnormality involving nigrosome-1 can be detected at 3T MR imaging with an accuracy of 94.6%. Due to the difficulty in diagnosis of early stage IPD, a loss of the swallow tail sign serves as a useful imaging biomarker to supplement the clinical diagnosis, as seen in our patient.

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