Imaging of the nigrostriatal system for evaluating the preclinical phase of Parkinson’s disease development: the utility of neuromelanin, diffusion MRI, and DAT-SPECT

2021 ◽  
Author(s):  
Hiroto Takahashi ◽  
Nobuo Kashiwagi ◽  
Atsuko Arisawa ◽  
Chisato Matsuo ◽  
Hiroki Kato ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Diffusion Tensor ◽  
Specific Binding ◽  
Mean Diffusivity ◽  
Substantia Nigra Pars Compacta ◽  
Nigrostriatal System ◽  
Sleep Behavior ◽  
Specific Binding Ratio ◽  
Preclinical Phase

Objectives: To assess the utility of examining the nigrostriatal system with magnetic resonance imaging (MRI) and dopamine transporter (DAT) imaging for evaluating the preclinical phase of Parkinson’s disease (PD). Methods: The subjects were 32 patients with early PD and a history of probable rapid eye movement sleep behavior disorder (RBD; PD group), 15 patients with idiopathic RBD (RBD group), and 24 age-matched healthy controls (HC group) who underwent neuromelanin and diffusion tensor MRI for analysis of the substantia nigra pars compacta (SNpc). The RBD and PD groups underwent DAT imaging. In the RBD group, totals of 39 MRI and 27 DAT imaging examinations were obtained longitudinally. For each value, intergroup differences and receiver-operating characteristic (ROC) analysis for diagnostic performance were examined statistically. Results: The neuromelanin value was significantly lower and the diffusion tensor values except fractional anisotropy were significantly higher in the RBD and PD groups than in the HC group. The DAT specific binding ratio (SBR) was significantly lower in the PD group than in the RBD group. The areas under the ROC curves (AUCs) for neuromelanin/mean diffusivity value in the SNpc were 0.76/0.82 for diagnosing RBD and 0.83/0.80 for diagnosing PD. The AUC for the SBR for discriminating PD from RBD was 0.87. Conclusions: MRI and DAT imaging may be useful for evaluating sequential nigrostriatal changes during the preclinical phase of PD. Advances in knowledge: MRI detects nigrostriatal changes in both RBD and early PD, and DAT imaging detects nigrostriatal changes during the transition to PD in RBD.

Asymmetric Dopaminergic Dysfunction in Brain-First versus Body-First Parkinson’s Disease Subtypes

2021 ◽  
pp. 1-11
Author(s):  
Karoline Knudsen ◽  
Tatyana D. Fedorova ◽  
Jacob Horsager ◽  
Katrine B. Andersen ◽  
Casper Skjærbæk ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
De Novo ◽  
Specific Binding ◽  
Asymmetry Index ◽  
The Body ◽  
Specific Binding Ratio ◽  
Dat Spect ◽  
Vagal Innervation ◽  
Nigrostriatal Degeneration

Background: We have hypothesized that Parkinson’s disease (PD) comprises two subtypes. Brain-first, where pathogenic α-synuclein initially forms unilaterally in one hemisphere leading to asymmetric nigrostriatal degeneration, and body-first with initial enteric pathology, which spreads through overlapping vagal innervation leading to more symmetric brainstem involvement and hence more symmetric nigrostriatal degeneration. Isolated REM sleep behaviour disorder has been identified as a strong marker of the body-first type. Objective: To analyse striatal asymmetry in [18F]FDOPA PET and [123I]FP-CIT DaT SPECT data from iRBD patients, de novo PD patients with RBD (PD +RBD) and de novo PD patients without RBD (PD - RBD). These groups were defined as prodromal body-first, de novo body-first, and de novo brain-first, respectively. Methods: We included [18F]FDOPA PET scans from 21 iRBD patients, 11 de novo PD +RBD, 22 de novo PD - RBD, and 18 controls subjects. Also, [123I]FP-CIT DaT SPECT data from iRBD and de novo PD patients with unknown RBD status from the PPPMI dataset was analysed. Lowest putamen specific binding ratio and putamen asymmetry index (AI) was defined. Results: Nigrostriatal degeneration was significantly more symmetric in patients with RBD versus patients without RBD or with unknown RBD status in both FDOPA (p = 0.001) and DaT SPECT (p = 0.001) datasets. Conclusion: iRBD subjects and de novo PD +RBD patients present with significantly more symmetric nigrostriatal dopaminergic degeneration compared to de novo PD - RBD patients. The results support the hypothesis that body-first PD is characterized by more symmetric distribution most likely due to more symmetric propagation of pathogenic α-synuclein compared to brain-first PD.

scholarly journals Levodopa-Responsive Primary Slow Orthostatic Tremor: A Premotor Sign of Parkinson’s Disease?

2020 ◽  
Vol 12 (1) ◽  
pp. 1-6
Author(s):  
Fumihito Yoshii ◽  
Wakoh Takahashi ◽  
Koji Aono
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Surface Electromyography ◽  
Specific Binding ◽  
Low Frequency ◽  
Orthostatic Tremor ◽  
Specific Binding Ratio ◽  
Dopaminergic Medication ◽  
Neurological Signs ◽  
Dat Spect

We present a case of primary orthostatic tremor (OT) responsive to dopaminergic medication. The patient was a 62-year-old woman, who had leg tremor on standing for 2 years. No parkinsonian or other neurological signs were observed. Surface electromyography of the quadriceps muscles showed regular 5–6 Hz muscle discharges. [123I]-FP-CIT DAT-SPECT imaging revealed decreased specific binding ratio values in the striatum compared with age-matched controls. Her leg tremor almost completely disappeared following administration of levodopa 200 mg and pramipexole 0.75 mg. Since her OT with low-frequency discharge was responsive to dopaminergic medication, we speculate that it may be a premotor sign of Parkinson’s disease.

scholarly journals Microstructural Abnormalities of Substantia Nigra in Parkinson’s disease: A Neuromelanin Sensitive MRI Atlas Based Study

2019 ◽  
Author(s):  
Apoorva Safai ◽  
Shweta Prasad ◽  
Jitender Saini ◽  
Pramod Kumar Pal ◽  
Madhura Ingalhalikar
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Diffusion Tensor ◽  
Region Of Interest ◽  
Substantia Nigra Pars Compacta ◽  
Microstructural Changes ◽  
Severity Scores ◽  
Mri Sequences ◽  
The Right

AbstractMicrostructural changes associated with degeneration of dopaminergic neurons of the substantia nigra pars compacta (SNc) in Parkinson’s disease (PD) have been studied using Diffusion Tensor Imaging (DTI). However, these studies show inconsistent results, mainly due to methodological variations in delineation of SNc. To mitigate this, our work aims to construct a probabilistic atlas of SNc based on a Neuromelanin sensitive MRI (NMS-MRI) sequence and demonstrate its applicability to investigate microstructural changes on a large dataset of PD. Using manual segmentation and deformable registrations, we create a novel SNc atlas in the MNI space using NMS-MRI sequences of 27 healthy controls (HC). We employ this atlas to evaluate the diffusivity and anisotropy measures, derived from diffusion MRI in the SNc of 135 patients with PD and 99 HCs. Our observations of significantly increased diffusivity measures provide evidence of microstructural abnormalities in PD. However, no changes in the anisotropy were observed. Moreover, the asymmetry in abnormalities is prominent as the left SNc showed significant increase in diffusivity, and a reduction in FA when compared to the right SNc. Further the diffusivity and FA values also demonstrated a trend when correlated with the PD severity scores. Overall, from this work we establish a normative baseline for the SNc region of interest using NMS-MRI while the application on PD data emphasizes on the contribution of diffusivity measures rather than anisotropy of white matter in PD.

scholarly journals White matter and nigral alterations in multiple system atrophy-parkinsonian type

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Takashi Ogawa ◽  
Taku Hatano ◽  
Koji Kamagata ◽  
Christina Andica ◽  
Haruka Takeshige-Amano ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
White Matter ◽  
Multiple System Atrophy ◽  
Volume Fraction ◽  
Diffusion Tensor ◽  
Free Water ◽  
Substantia Nigra Pars Compacta ◽  
Healthy Controls ◽  
Cerebellar Peduncle

AbstractMultiple system atrophy (MSA) is classified into two main types: parkinsonian and cerebellar ataxia with oligodendrogliopathy. We examined microstructural alterations in the white matter and the substantia nigra pars compacta (SNc) of patients with MSA of parkinsonian type (MSA-P) using multishell diffusion magnetic resonance imaging (dMRI) and myelin sensitive imaging techniques. Age- and sex-matched patients with MSA-P (n = 21, n = 10 first and second cohorts, respectively), Parkinson’s disease patients (n = 19, 17), and healthy controls (n = 20, 24) were enrolled. Magnetization transfer saturation imaging (MT-sat) and dMRI were obtained using 3-T MRI. Measurements obtained from diffusion tensor imaging (DTI), free-water elimination DTI, neurite orientation dispersion and density imaging (NODDI), and MT-sat were compared between groups. Tract-based spatial statistics analysis revealed differences in diffuse white matter alterations in the free-water fractional volume, myelin volume fraction, and intracellular volume fraction between the patients with MSA-P and healthy controls, whereas free-water and MT-sat differences were limited to the middle cerebellar peduncle in comparison with those with Parkinson’s disease. Region-of-interest analysis of white matter and SNc revealed significant differences in the middle and inferior cerebellar peduncle, pontine crossing tract, corticospinal tract, and SNc between the MSA-P and healthy controls and/or Parkinson’s disease patients. Our results shed light on alterations to brain microstructure in MSA.

scholarly journals White Matter Microstructural Integrity and Executive Function in Parkinson's Disease

2013 ◽  
Vol 19 (3) ◽  
pp. 349-354 ◽  
Author(s):  
Catherine Gallagher ◽  
Brian Bell ◽  
Barbara Bendlin ◽  
Matthew Palotti ◽  
Ozioma Okonkwo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Executive Function ◽  
White Matter ◽  
Diffusion Tensor ◽  
A Priori ◽  
Mean Diffusivity ◽  
Pathological Process ◽  
Intracranial Volume ◽  
Mean Values

AbstractRecent studies suggest that white matter abnormalities contribute to both motor and non-motor symptoms of Parkinson's disease. The present study was designed to investigate the degree to which diffusion tensor magnetic resonance imaging (DTI) indices are related to executive function in Parkinson's patients. We used tract-based spatial statistics to compare DTI data from 15 patients to 15 healthy, age- and education-matched controls. We then extracted mean values of fractional anisotropy (FA) and mean diffusivity (MD) within an a priori frontal mask. Executive function composite Z scores were regressed against these DTI indices, age, and total intracranial volume. In Parkinson's patients, FA was related to executive composite scores, and both indices were related to Stroop interference scores. We conclude that white matter microstructural abnormalities contribute to cognitive deficits in Parkinson's disease. Further work is needed to determine whether these white matter changes reflect the pathological process or a clinically important comorbidity. (JINS, 2013, 19, 1–6)

scholarly journals Corpus Callosum and Cingulum Tractography in Parkinson's Disease

2010 ◽  
Vol 37 (5) ◽  
pp. 595-600 ◽  
Author(s):  
Katie Wiltshire ◽  
Luis Concha ◽  
Myrlene Gee ◽  
Thomas Bouchard ◽  
Christian Beaulieu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
White Matter ◽  
Corpus Callosum ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Imaging Method ◽  
Motor Symptoms ◽  
Mri Scans

Background:In Parkinson's disease (PD) cell loss in the substantia nigra is known to result in motor symptoms; however widespread pathological changes occur and may be associated with non-motor symptoms such as cognitive impairment. Diffusion tensor imaging is a quantitative imaging method sensitive to the micro-structure of white matter tracts.Objective:To measure fractional anisotropy (FA) and mean diffusivity (MD) values in the corpus callosum and cingulum pathways, defined by diffusion tensor tractography, in patients with PD, PD with dementia (PDD) and controls and to determine if these measures correlate with Mini-Mental Status Examination (MMSE) scores in parkinsonian patients.Methods:Patients with PD (17 Males [M], 12 Females [F]), mild PDD (5 M, 1F) and controls (8 M, 7F) underwent cognitive testing and MRI scans. The corpus callosum was divided into four regions and the cingulum into two regions bilaterally to define tracts using the program DTIstudio (Johns Hopkins University) using the fiber assignment by continuous tracking algorithm. Volumetric MRI scans were used to measure white and gray matter volumes.Results:Groups did not differ in age or education. There were no overall FA or MD differences between groups in either the corpus callosum or cingulum pathways. In PD subjects the MMSE score correlated with MD within the corpus callosum. These findings were independent of age, sex and total white matter volume.Conclusions:The data suggest that the corpus callosum or its cortical connections are associated with cognitive impairment in PD patients.

scholarly journals Automated Assessment of the Substantia Nigra Pars Compacta in Parkinson’s Disease: A Diffusion Tensor Imaging Study

2021 ◽  
Vol 11 (11) ◽  
pp. 1235
Author(s):  
Niels Bergsland ◽  
Laura Pelizzari ◽  
Maria Marcella Laganá ◽  
Sonia Di Tella ◽  
Federica Rossetto ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Diffusion Tensor Imaging ◽  
Substantia Nigra ◽  
Rating Scale ◽  
Diffusion Tensor ◽  
Imaging Study ◽  
Substantia Nigra Pars Compacta ◽  
Disease Rating ◽  
Magnetic Resonance Imaging Mri

The substantia nigra (SN) pars compacta (SNpc) and pars reticulata (SNpr) are differentially affected in Parkinson’s disease (PD). Separating the SNpc and SNpr is challenging with standard magnetic resonance imaging (MRI). Diffusion tensor imaging (DTI) allows for the characterization of SN microstructure in a non-invasive manner. In this study, 29 PD patients and 28 healthy controls (HCs) were imaged with 1.5T MRI for DTI. Images were nonlinearly registered to standard space and SNpc and SNpr DTI parameters were measured. ANCOVA and receiver operator characteristic (ROC) analyses were performed. Clinical associations were assessed with Spearman correlations. Multiple corrections were controlled for false discovery rate. PD patients presented with significantly increased SNpc axial diffusivity (AD) (1.207 ± 0.068 versus 1.156 ± 0.045, p = 0.024), with ROC analysis yielding an under the curve of 0.736. Trends with Unified Parkinson’s Disease Rating Scale (UPDRS) III scores were identified for SNpc MD (rs = 0.449), AD (rs = 0.388), and radial diffusivity (rs = 0.391) (all p < 0.1). A trend between baseline SNpr MD and H&Y change (rs = 0.563, p = 0.081) over 2.9 years of follow-up was identified (n = 14). In conclusion, SN microstructure shows robust, clinically meaningful associations in PD.

scholarly journals Melatonin as a Chronobiotic and Cytoprotective Agent in Parkinson’s Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Santiago Pérez-Lloret ◽  
Daniel P. Cardinali
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Clinical Studies ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Substantia Nigra Pars Compacta ◽  
Double Blind ◽  
Sleep Behavior ◽  
Day Range

This article discusses the role that melatonin may have in the prevention and treatment of Parkinson’s disease (PD). In parkinsonian patients circulating melatonin levels are consistently disrupted and the potential therapeutic value of melatonin on sleep disorders in PD was examined in a limited number of clinical studies using 2–5 mg/day melatonin at bedtime. The low levels of melatonin MT1 and MT2 receptor density in substantia nigra and amygdala found in PD patients supported the hypothesis that the altered sleep/wake cycle seen in PD could be due to a disrupted melatonergic system. Motor symptomatology is seen in PD patients when about 75% of the dopaminergic cells in the substantia nigra pars compacta region degenerate. Nevertheless, symptoms like rapid eye movement (REM) sleep behavior disorder (RBD), hyposmia or depression may precede the onset of motor symptoms in PD for years and are index of worse prognosis. Indeed, RBD patients may evolve to an α-synucleinopathy within 10 years of RBD onset. Daily bedtime administration of 3–12 mg of melatonin has been demonstrated effective in RDB treatment and may halt neurodegeneration to PD. In studies on animal models of PD melatonin was effective to curtail symptomatology in doses that allometrically projected to humans were in the 40–100 mg/day range, rarely employed clinically. Therefore, double-blind, placebo-controlled clinical studies are urgently needed in this respect.

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