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1.
Curr Neurol Neurosci Rep ; 21(6): 24, 2021 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-33817766

RESUMO

PURPOSE OF REVIEW: There has been an exponential growth in functional connectomics research in neurodegenerative disorders. This review summarizes the recent findings and limitations of the field in Parkinson's disease (PD) and atypical parkinsonian syndromes. RECENT FINDINGS: Increasingly more sophisticated methods ranging from seed-based to network and whole-brain dynamic functional connectivity have been used. Results regarding the disruption in the functional connectome vary considerably based on disease severity and phenotypes, and treatment status in PD. Non-motor symptoms of PD also link to the dysfunction in heterogeneous networks. Studies in atypical parkinsonian syndromes are relatively scarce. An important clinical goal of functional connectomics in neurodegenerative disorders is to establish the presence of pathology, track disease progression, predict outcomes, and monitor treatment response. The obstacles of reliability and reproducibility in the field need to be addressed to improve the potential of the functional connectome as a biomarker for these purposes in PD and atypical parkinsonian syndromes.


Assuntos
Conectoma , Atrofia de Múltiplos Sistemas , Doença de Parkinson , Transtornos Parkinsonianos , Paralisia Supranuclear Progressiva , Humanos , Doença de Parkinson/diagnóstico por imagem , Transtornos Parkinsonianos/diagnóstico por imagem , Reprodutibilidade dos Testes
2.
Artigo em Inglês | MEDLINE | ID: mdl-33670940

RESUMO

The neurobiology of Parkinson's disease and its progression has been investigated during the last few decades. Braak et al. proposed neuropathological stages of this disease based on the recognizable topographical extent of Lewy body lesions. This pathological process involves specific brain areas with an ascending course from the brain stem to the cortex. Post-mortem studies are of importance to better understand not only the progression of motor symptoms, but also the involvement of other domains, including cognition and behavior. The correlation between the neuropathological expansion of the disease and the clinical phases remains demanding. Neuroimaging, including magnetic resonance imaging (MRI), positron emission tomography (PET), and single photon emission computed tomography (SPECT), could help to bridge this existing gap by providing in vivo evidence of the extension of the disorders. In the last decade, we observed an overabundance of reports regarding the sensitivity of neuroimaging techniques. All these studies were aimed at improving the accuracy of Parkinson's disease (PD) diagnosis and discriminating it from other causes of parkinsonism. In this review, we look at the recent literature concerning PD and address the new frontier of diagnostic accuracy in terms of identification of early stages of the disease and conventional neuroimaging techniques that, in vivo, are capable of photographing the basal ganglia network and its cerebral connections.


Assuntos
Doença de Parkinson , Transtornos Parkinsonianos , Encéfalo/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Neuroanatomia , Neuroimagem , Doença de Parkinson/diagnóstico por imagem
3.
Medicine (Baltimore) ; 100(6): e24631, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33578580

RESUMO

RATIONALE: The Pisa syndrome (PS) is defined as a kind of reversible postural deformity which causes a lateral trunk flexion of 10 degrees or more. A prevalence of approximately 7.4% to 10.3% of patients with Parkinson disease (PD) also have PS. Though unbalanced function of the basal ganglia network and impaired visual-spatial functions including parietal cortices in PS is known, the pathophysiology of PS remains to be unclear. PATIENT CONCERNS: A 67-year-old male patient with PD visited our Rehabilitation outpatient department because of his trunk which involuntarily deviated to the left side when he stood up. DIAGNOSES: Based on the history, physical examination, X-ray images, Tc-99m brain TRODAT-1 single-photon emission computed tomography (SPECT), and regional cerebral perfusion Tc-99m ethyl cysteinate dimer SPECT, the patient was diagnosed with PD with PS. INTERVENTIONS: The patient refused our recommendation of admission for pharmaceutical treatment due to personal reasons and was only willing to accept physical training programs at our outpatient department. OUTCOMES: We arranged functional neuroimaging of the brain to survey possible neurologic deficits. The patient's images of ethyl cysteinate dimer SPECT and TRODAT SPECT showed abnormalities, including hypoperfusion and diminished dopamine transporter uptake, in the areas of the basal ganglia network and other brain regions. LESSONS: Based on previous literature and the imaging of our patient, we hypothesize that PS results from unbalanced function of the basal ganglia network and impaired visual-spatial functions of bilateral parietal cortices.


Assuntos
Doença de Parkinson/diagnóstico por imagem , Idoso , Humanos , Masculino , Neuroimagem , Compostos de Organotecnécio , Doença de Parkinson/reabilitação , Compostos Radiofarmacêuticos , Síndrome , Tomografia Computadorizada de Emissão de Fóton Único , Tropanos
4.
Medicine (Baltimore) ; 100(7): e24837, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33607852

RESUMO

ABSTRACT: Dysautonomia is common in patients with Parkinson disease (PD) since disease early phase. Scales for Outcomes in Parkinson's disease - Autonomic (SCOPA-AUT) is a well-designed scale assessing the autonomic dysfunctions of PD patients. Our objectives were to examine the autonomic dysfunction in PD and scan without evidence of dopaminergic deficit (SWEDD) patients and to assess the correlation of autonomic dysfunctions with cerebrospinal fluid (CSF) biomarkers.An analysis of the Parkinson's Progression Markers Initiative (PPMI) data including 414 PD patients, 60 SWEDD patients, and 170 healthy controls (HCs) with baseline CSF biomarker measurements and SCOPA-AUT assessments was presented. Autonomic symptoms including gastrointestinal, urinary, cardiovascular, pupillomotor, thermoregulatory and sexual dysfunctions were assessed by SCOPA-AUT scales. Spearman correlation test was used to examine the correlations between CSF measurements and each section of SCOPA-AUT scales in HCs and subjects with PD or SWEDD.More severe autonomic dysfunctions were observed in patients with SWEDD than those with PD (P < .001). Specifically, patients with PD have lower scores on the urinary scale [4 (0-17) vs 5 (1-18)], pupillomotor scale [0 (0-3) vs 0 (0-3)], thermoregulatory scale [0 (0-4) vs 1.5 (0-10)] and sexual scale [1 (0-6) vs 2 (0-6)] compared with SWEDD patients. Thermoregulatory dysfunction scores were found correlated with CSF α-syn levels in SWEDD group, and gastrointestinal dysfunction scores were correlated with CSF Abeta1-42 in PD group. Additionally, urinary dysfunction scores were correlated with CSF total tau and tau phosphorylated at threonine 181(p-tau181) levels in both HCs and PD patients.


Assuntos
Biomarcadores/líquido cefalorraquidiano , Dopamina/deficiência , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/metabolismo , Idoso , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Sistema Nervoso Autônomo/fisiopatologia , Doenças do Sistema Nervoso Autônomo/líquido cefalorraquidiano , Doenças do Sistema Nervoso Autônomo/diagnóstico , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Regulação da Temperatura Corporal/fisiologia , Estudos de Casos e Controles , Feminino , Gastroenteropatias/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/líquido cefalorraquidiano , Doença de Parkinson/fisiopatologia , Disautonomias Primárias/etiologia , Índice de Gravidade de Doença , Inquéritos e Questionários , Doenças Urológicas/metabolismo
5.
Nat Commun ; 12(1): 779, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536430

RESUMO

MR-guided focused ultrasound (MRgFUS), in combination with intravenous microbubble administration, has been applied for focal temporary BBB opening in patients with neurodegenerative disorders and brain tumors. MRgFUS could become a therapeutic tool for drug delivery of putative neurorestorative therapies. Treatment for Parkinson's disease with dementia (PDD) is an important unmet need. We initiated a prospective, single-arm, non-randomized, proof-of-concept, safety and feasibility phase I clinical trial (NCT03608553), which is still in progress. The primary outcomes of the study were to demonstrate the safety, feasibility and reversibility of BBB disruption in PDD, targeting the right parieto-occipito-temporal cortex where cortical pathology is foremost in this clinical state. Changes in ß-amyloid burden, brain metabolism after treatments and neuropsychological assessments, were analyzed as exploratory measurements. Five patients were recruited from October 2018 until May 2019, and received two treatment sessions separated by 2-3 weeks. The results are set out in a descriptive manner. Overall, this procedure was feasible and reversible with no serious clinical or radiological side effects. We report BBB opening in the parieto-occipito-temporal junction in 8/10 treatments in 5 patients as demonstrated by gadolinium enhancement. In all cases the procedures were uneventful and no side effects were encountered associated with BBB opening. From pre- to post-treatment, mild cognitive improvement was observed, and no major changes were detected in amyloid or fluorodeoxyglucose PET. MRgFUS-BBB opening in PDD is thus safe, reversible, and can be performed repeatedly. This study provides encouragement for the concept of BBB opening for drug delivery to treat dementia in PD and other neurodegenerative disorders.


Assuntos
Barreira Hematoencefálica/diagnóstico por imagem , Demência/diagnóstico por imagem , Doença de Parkinson/diagnóstico por imagem , Ultrassonografia/métodos , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/terapia , Barreira Hematoencefálica/metabolismo , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/terapia , Meios de Contraste , Demência/terapia , Estudos de Viabilidade , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Microbolhas , Avaliação de Resultados em Cuidados de Saúde/métodos , Doença de Parkinson/terapia , Tomografia por Emissão de Pósitrons/métodos , Estudos Prospectivos
6.
JAMA Ophthalmol ; 139(2): 182-188, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33355613

RESUMO

Importance: Noninvasive retinal imaging may detect structural changes associated with Parkinson disease (PD) and may represent a novel biomarker for disease detection. Objective: To characterize alterations in the structure and microvasculature of the retina and choroid in eyes of individuals with PD and compare them with eyes of age- and sex-matched cognitively healthy control individuals using optical coherence tomography (OCT) and OCT angiography (OCTA). Design, Setting, and Participants: This cross-sectional study was conducted at the Duke Neurological Disorders Clinic in Durham, North Carolina. Individuals aged 50 years or older with a diagnosis of PD were eligible for inclusion and underwent an evaluation and diagnosis confirmation before enrollment. Control individuals aged 50 years or older and without subjective cognitive dysfunction, a history of tremor, or evidence of motor dysfunction consistent with parkinsonism were solicited from the clinic or the Duke Alzheimer's Disease Prevention Registry. Individuals with diabetes, glaucoma, retinal pathology, other dementias, and corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity worse than 20/40 Snellen were excluded. Data were analyzed between January 1, 2020, and March 30, 2020. Exposures: All participants underwent OCT and OCTA imaging. Main Outcomes and Measures: Generalized estimating equation analysis was used to characterize the association between imaging parameters and PD diagnosis. Superficial capillary plexus vessel density (VD) and perfusion density (PFD) were assessed within the ETDRS 6 × 6-mm circle, 6 × 6-mm inner ring, and 6 × 6-mm outer ring, as was the foveal avascular zone area. Peripapillary retinal nerve fiber layer thickness, macular ganglion cell-inner plexiform layer thickness, central subfield thickness, subfoveal choroidal thickness, total choroidal area, luminal area, and choroidal vascularity index (CVI) were measured. Results: A total of 124 eyes of 69 participants with PD (39 men [56.5%]; mean [SD] age, 71.7 [7.0] years) and 248 eyes of 137 control participants (77 men [56.2%]; mean [SD] age, 70.9 [6.7] years) were analyzed. In the 6 × 6-mm ETDRS circle, VD (ß coefficient = 0.37; 95% CI, 0.04-0.71; P = .03) and PFD (ß coefficient = 0.009; 95% CI, 0.0003-0.018; P = .04) were lower in eyes of participants with PD. In the inner ring of the 6 × 6-mm ETDRS circle, VD (ß coefficient = 0.61; 95% CI, 0.20-1.02; P = .003) and PFD (ß coefficient = 0.015; 95% CI, 0.005-0.026; P = .004) were lower in eyes of participants with PD. Total choroidal area (ß coefficient = -1.74 units2; 95% CI, -3.12 to -0.37 units2; P = .01) and luminal area (ß coefficient = -1.02 units2; 95% CI, -1.86 to -0.18 units2; P = .02) were greater, but CVI was lower (ß coefficient = 0.5%; 95% CI, 0.2%-0.8%; P < .001) in eyes of individuals with PD. Conclusions and Relevance: This study found that individuals with PD had decreased retinal VD and PFD as well as choroidal structural changes compared with age- and sex-matched control participants. Given the observed population differences in these noninvasive retinal biomarkers, further research into their clinical utility in PD is needed.


Assuntos
Angiografia , Corioide/irrigação sanguínea , Corioide/diagnóstico por imagem , Microvasos/diagnóstico por imagem , Doença de Parkinson/diagnóstico por imagem , Vasos Retinianos/diagnóstico por imagem , Tomografia de Coerência Óptica , Idoso , Estudos de Casos e Controles , Corioide/fisiopatologia , Estudos Transversais , Feminino , Humanos , Masculino , Microvasos/fisiopatologia , Pessoa de Meia-Idade , North Carolina , Doença de Parkinson/fisiopatologia , Valor Preditivo dos Testes , Estudos Prospectivos , Fluxo Sanguíneo Regional , Vasos Retinianos/fisiopatologia
7.
Clin Nucl Med ; 46(2): 119-124, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33323728

RESUMO

INTRODUCTION: Degeneration of dopaminergic, nigrostriatal neurons is the hallmark of Parkinson disease (PD), and PET quantification of dopamine transporters is a widely accepted method for differential diagnosis between idiopathic PD and essential tremor. [18F]PR04.MZ is a new PET tracer with excellent imaging properties allowing for precise quantification of striatal and extrastriatal dopamine transporter. Here we describe our initial experience with [18F]PR04.MZ PET/CT in a larger cohort of healthy controls and PD patients as a proof-of-concept study for this tracer. METHODS: Eighteen healthy subjects, 19 early PD patients (Hoehn-Yahr I-II), and 13 moderate-advanced PD patients (Hoehn-Yahr III-IV) underwent static PET/CT scans 60 to 90 minutes after injection of 5.16 ± 1.03 mCi (191 ± 38 MBq) [18F]PR04.MZ. Specific binding ratios (SBRs) were calculated for caudate nucleus, anterior putamen, posterior putamen, substantia nigra (SNpc), compared between different groups and correlated with clinical ratings. RESULTS: [18F]PR04.MZ showed very high and specific uptake in the putamen, caudate, and substantia nigra pars compacta and very low nonspecific binding in other brain regions, and SBR values for the control group were 22.3 ± 4.1, 19.1 ± 3.5, and 5.4 ± 1.2, respectively. A reduction of SBR values was observed in all regions and in both initial and moderate PD, ranging from 35% to 89% (P < 0.001). The observed pattern of reduction was posterior putamen > anterior putamen > substantia nigra pars compacta > caudate, with contralateral posterior putamen being the most affected region. Rostrocaudal depletion gradient was evident in all PD patients and progression correlated with motor manifestations. CONCLUSIONS: [18F]PR04.MZ PET/CT is a highly sensitive imaging modality for the detection of dopaminergic deficit in nigrostriatal pathways in PD.


Assuntos
Neurônios/patologia , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/patologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Substância Negra/patologia , Idoso , Estudos de Coortes , Dopamina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurônios/metabolismo , Doença de Parkinson/metabolismo
8.
Medicine (Baltimore) ; 99(51): e23395, 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33371068

RESUMO

BACKGROUND: Parkinson's disease (PD) has a high incidence in the elderly, and the late stage seriously affects the daily life of the patients. Most of the initial symptoms of PD are not obvious or atypical, which brings difficulties to the early diagnosis. Replacement therapy and neuroprotection after early diagnosis can significantly improve the prognosis and quality of life of patients. More and more evidence shows that 11C-2ß-carbomethoxy-3ß-(4-fluorophenyl) tropane positron emission tomography ( 11C-CFT PET) combined with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) can effectively improve the accuracy of early diagnosis. However, there is no consistent conclusion at present. The purpose of this study is to evaluate the efficacy of 11C-CFT PET combined with 18F-FDG PET in the diagnosis of early PD. METHODS: We will search 7 electronic databases (PubMed, EMBASE, Web of Science, Cochrane library, PsycINFO, AMED, Scopus), ongoing trials and grey literature to collect related randomized controlled trials and will use Review Manager Software 5.2 and STATA Software 16.0 for analysis and synthesis. RESULTS: We will integrate the existing randomized controlled trials to evaluate the value of 11C-CFT PET combined with 18F-FDG PET in the diagnosis of early PD. CONCLUSION: Our study may prove that 11C-CFT PET combined with 18F-FDG PET can effectively diagnose early PD. REGISTRATION NUMBER: International Prospective Register of Systematic Reviews (PROSPERO): CRD42020203442.


Assuntos
Fluordesoxiglucose F18/administração & dosagem , Doença de Parkinson/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/administração & dosagem , Tropanos/administração & dosagem , Humanos , Imagem Multimodal , Doença de Parkinson/diagnóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Sensibilidade e Especificidade , Índice de Gravidade de Doença
9.
Vestn Oftalmol ; 136(5. Vyp. 2): 191-196, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33063963

RESUMO

One of the research directions of the so-called non-motor manifestations of Parkinson's disease (PD) is associated with the assessment of structural and functional changes in the organ of vision. An assessment of the state of thin non-myelinated corneal nerve fibers (CNF) in Parkinson's disease seems to be promising considering the neurodegenerative nature of the disease, as well as the possibility of objective intravital assessment of both functional and structural changes in CNF. PURPOSE: To analyze the changes in the course and structure of corneal nerve fibers in the early stages of Parkinson's disease based on an objective algorithm of in vivo corneal confocal microscopy (CCM). MATERIAL AND METHODS: The study was conducted on a group of 16 patients aged 39 to 66 years with verified diagnosis of PD. In addition to standard neurological and ophthalmological examinations, all patients underwent IVCCM on a Heidelberg Retinal Tomograph device with special Rostock Cornea Module (HRT3 RCM), followed by processing of the obtained images using a uniquely designed analysis algorithm. RESULTS: A significant decrease in the directional anisotropy coefficient and an increase in the directional symmetry coefficient of the nerve fibers of the cornea were established (average values 3.15±1.08 and 0.92±0.04, respectively); in healthy individuals of the identical age range these indicators are 3.5±0.85 and 0.86±0.11, respectively. In addition, qualitative structural changes were noted, which consisted of an increase in the number of branches from the main nerve trunks, an increase in the tortuosity of CNF, multidirectionality, and "beaded" shape. In 9 cases, the presence of macrophages was revealed - dendritic Langerhans cells, which is an indirect sign of the inflammatory process. CONCLUSION: The preliminary nature of the results obtained in this study and the need for further research in this area are related, on the one hand, to a small sample of observations and, on the other hand, to the criterion used to assess the status of CNF based on a comparative analysis with conditionally normal indicators. In the future, in order to solve the problem of the uniqueness of changes in CNF and the possibility of using these changes as a marker for PD progression, longitudinal studies are required to reveal the presence or absence of a correlation between the stage of the disease, the results of known monitoring methods (e.g. electromyography) and quantitative indicators of the status of CNF.


Assuntos
Doença de Parkinson , Adulto , Idoso , Anisotropia , Córnea/diagnóstico por imagem , Humanos , Microscopia Confocal , Pessoa de Meia-Idade , Fibras Nervosas , Doença de Parkinson/diagnóstico por imagem
11.
Acta Neurol Scand ; 142(4): 385-391, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32914881

RESUMO

BACKGROUND: Idiopathic Parkinson's disease (PD) is characterized by clinical motor symptoms including hypokinesia, rigidity and tremor. In addition to the movement disorder, cognitive deficits are commonly described. In the present study, we applied FP-CIT SPECT to investigate the impact of nigrostriatal dopaminergic degeneration on cognitive function in PD patients. METHODS: Fifty-four PD patients underwent [123I]FP-CIT SPECT and CERAD (Consortium to Establish a Registry for Alzheimer's Disease) testing. FP-CIT SPECT visualized the density of presynaptic dopamine transporters in both striata, each subdivided into a limbic, executive and sensorimotor subregion according to the atlas of Tziortzi et al (Cereb Cortex 24, 2014, 1165). CERAD testing quantified cognitive function. RESULTS: In the CERAD testing, PD patients exhibited deficits in the domains of semantic memory, attention, visuospatial function, non-verbal memory and executive function. After correction for multiple testing, the performance of the subtests Figure Recall and Trail-Making Test A correlated significantly with FP-CIT uptake into the ipsilateral executive subregion. The performance of the subtest Figure Saving correlated significantly with FP-CIT uptake into the contralateral executive subregion. CONCLUSIONS: The significant correlation between cognitive function and density of nigrostriatal dopamine transporters, as assessed by FP-CIT SPECT, indicate that striatal dopaminergic pathways-primarily the executive striatal subregion-are relevant to cognitive processing in PD.


Assuntos
Cognição , Corpo Estriado/diagnóstico por imagem , Doença de Parkinson/diagnóstico por imagem , Compostos Radiofarmacêuticos , Tomografia Computadorizada de Emissão de Fóton Único , Tropanos , Corpo Estriado/metabolismo , Feminino , Humanos , Masculino , Doença de Parkinson/fisiopatologia , Tremor
12.
Neurology ; 95(11): e1445-e1460, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32817178

RESUMO

OBJECTIVE: To identify biotypes in patients with newly diagnosed Parkinson disease (PD) and to test whether these biotypes could explain interindividual differences in longitudinal progression. METHODS: In this longitudinal analysis, we use a data-driven approach clustering PD patients from the Parkinson's Progression Markers Initiative (n = 314, age 61.0 ± 9.5, years 34.1% female, 5 years of follow-up). Voxel-level neuroanatomic features were estimated with deformation-based morphometry (DBM) of T1-weighted MRI. Voxels with deformation values that were significantly correlated (p < 0.01) with clinical scores (Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale Parts I-III and total score, tremor score, and postural instability and gait difficulty score) at baseline were selected. Then, these neuroanatomic features were subjected to hierarchical cluster analysis. Changes in the longitudinal progression and neuroanatomic pattern were compared between different biotypes. RESULTS: Two neuroanatomic biotypes were identified: biotype 1 (n = 114) with subcortical brain volumes smaller than heathy controls and biotype 2 (n = 200) with subcortical brain volumes larger than heathy controls. Biotype 1 had more severe motor impairment, autonomic dysfunction, and much worse REM sleep behavior disorder than biotype 2 at baseline. Although disease durations at the initial visit and follow-up were similar between biotypes, patients with PD with smaller subcortical brain volume had poorer prognosis, with more rapid decline in several clinical domains and in dopamine functional neuroimaging over an average of 5 years. CONCLUSION: Robust neuroanatomic biotypes exist in PD with distinct clinical and neuroanatomic patterns. These biotypes can be detected at diagnosis and predict the course of longitudinal progression, which should benefit trial design and evaluation.


Assuntos
Progressão da Doença , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/metabolismo , Idoso , Análise por Conglomerados , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/classificação , Tomografia por Emissão de Pósitrons/tendências , Tomografia Computadorizada por Raios X/tendências
13.
Medicine (Baltimore) ; 99(31): e21403, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756136

RESUMO

BACKGROUND: A growing number of studies have used surface-based morphometry (SBM) analyses to investigate gray matter cortical thickness (CTh) abnormalities in Parkinson disease (PD). However, the results across studies are inconsistent and have not been systematically reviewed. A clear picture of CTh alterations in PD remains lacked. Coordinate-based meta-analysis (CBMA) is a powerful tool to quantitatively integrate the results of individual voxel-based neuroimaging studies to identify the functional or structural neural substrates of particular neuropsychiatric disorders. Recently, CBMA has been updated for integrating SBM studies. METHODS: The online databases PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang, and SinoMed were comprehensively searched without language limitations from the database inception to February 2, 2020. We will include all SBM studies that compared regional CTh between patients with idiopathic PD and healthy control subjects at the whole-cortex level using Seed-based d Mapping with Permutation of Subject Images (SDM-PSI). In addition to the main CBMA, we will conduct several supplementary analyses to test the robustness of the results, such as jackknife analyses, subgroup analyses, heterogeneity analyses, publication bias analyses, and meta-regression analyses. RESULTS: This CBMA will offer the latest evidence of CTh alterations in PD. CONCLUSIONS: Consistent and robust evidence of CTh alterations will feature brain morphometry of PD and may facilitate biomarker development. PROSPERO REGISTRATION NUMBER: CRD42020148775.


Assuntos
Córtex Cerebral/fisiopatologia , Doença de Parkinson/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Bases de Dados Factuais , Humanos , Neuroimagem , Doença de Parkinson/diagnóstico por imagem , Análise de Regressão
14.
Artigo em Inglês | MEDLINE | ID: mdl-32722623

RESUMO

Purpose: Risk of falls is a common sequela affecting patients with Parkinson's disease (PD). Although motor impairment and dementia are correlated with falls, associations of brain structure and cognition deficits with falls remain unclear. Material and Methods: Thirty-five PD patients with dementia (PDD), and 37 age- and sex-matched healthy subjects were recruited for this study. All participants received structural magnetic resonance imaging (MRI) scans, and disease severity and cognitive evaluations. Additionally, patient fall history was recorded. Regional structural differences between PDD with and without fall groups were performed using voxel-based morphometry processing. Stepwise logistic regression analysis was used to predict the fall risk in PDD patients. Results: The results revealed that 48% of PDD patients experienced falls. Significantly lower gray matter volume (GMV) in the left calcarine and right inferior frontal gyrus in PDD patients with fall compared to PDD patients without fall were noted. The PDD patients with fall exhibited worse UPDRS-II scores compared to PDD patients without fall and were negatively correlated with lower GMV in the left calcarine (p/r = 0.004/-0.492). Furthermore, lower GMV in the left calcarine and right inferior frontal gyrus correlated with poor attention and executive functional test scores. Multiple logistic regression analysis showed that the left calcarine was the only variable (p = 0.004, 95% CI = 0.00-0.00) negatively associated with the fall event. Conclusions: PDD patients exhibiting impaired motor function, lower GMV in the left calcarine and right inferior frontal gyrus, and notable cognitive deficits may have increased risk of falls.


Assuntos
Acidentes por Quedas , Demência/diagnóstico por imagem , Substância Cinzenta/anatomia & histologia , Doença de Parkinson/diagnóstico por imagem , Idoso , Encéfalo/diagnóstico por imagem , Função Executiva , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
15.
Neurology ; 95(11): e1461-e1470, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32651292

RESUMO

OBJECTIVE: We tested the hypothesis that there are 2 distinct phenotypes of Parkinson tremor, based on interindividual differences in the response of resting tremor to dopaminergic medication. We also investigated whether this pattern is specific to tremor by comparing interindividual differences in the dopamine response of tremor to that of bradykinesia. METHODS: In this exploratory study, we performed a levodopa challenge in 76 tremulous patients with Parkinson tremor. Clinical scores (Movement Disorders Society-sponsored version of the Unified Parkinson's Disease Rating Scale part III) were collected "off" and "on" a standardized dopaminergic challenge (200/50 mg dispersible levodopa-benserazide). In both sessions, resting tremor intensity was quantified using accelerometry, both during rest and during cognitive coactivation. Bradykinesia was quantified using a speeded keyboard test. We calculated the distribution of dopamine-responsiveness for resting tremor and bradykinesia. In 41 patients, a double-blinded, placebo-controlled dopaminergic challenge was repeated after approximately 6 months. RESULTS: The dopamine response of resting tremor, but not bradykinesia, significantly departed from a normal distribution. A cluster analysis on 3 clinical and electrophysiologic markers of tremor dopamine-responsiveness revealed 3 clusters: dopamine-responsive, intermediate, and dopamine-resistant tremor. A repeated levodopa challenge after 6 months confirmed this classification. Patients with dopamine-responsive tremor had greater disease severity and tended to have a higher prevalence of dyskinesia. CONCLUSION: Parkinson resting tremor can be divided into 3 partially overlapping phenotypes, based on the dopamine response. These tremor phenotypes may be associated with different underlying pathophysiologic mechanisms, requiring a different therapeutic approach.


Assuntos
Antiparkinsonianos/uso terapêutico , Dopaminérgicos/uso terapêutico , Resistência a Medicamentos/efeitos dos fármacos , Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Tremor/tratamento farmacológico , Acelerometria , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Resistência a Medicamentos/fisiologia , Feminino , Seguimentos , Humanos , Hipocinesia/diagnóstico por imagem , Hipocinesia/tratamento farmacológico , Hipocinesia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/fisiopatologia , Resultado do Tratamento , Tremor/diagnóstico por imagem , Tremor/fisiopatologia
16.
BMC Neurol ; 20(1): 262, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32605601

RESUMO

BACKGROUND: In this study, we explored whether the proposed short-echo-time magnitude (setMag) image derived from quantitative susceptibility mapping (QSM) could resemble NM-MRI image in substantia nigra (SN), by quantitatively comparing the spatial similarity and diagnosis performances for Parkinson's disease (PD). METHODS: QSM and NM-MRI were performed in 18 PD patients and 15 healthy controls (HCs). The setMag images were calculated using the short-echo-time magnitude images. Bilateral hyperintensity areas of SN (SNhyper) were manually segmented on setMag and NM-MRI images by two raters in a blinded manner. The inter-rater reliability was evaluated by the intraclass correlation coefficients (ICC) and the Dice similarity coefficient (DSC). Then the inter-modality (i.e. setMag and NM-MRI) spatial similarity was quantitatively assessed using DSC and volume of the consensual voxels identified by both of two raters. The performances of mean SNhyper volume for PD diagnosis on setMag and NM-MRI images were evaluated using receiver operating characteristic (ROC) analysis. RESULTS: The SNhyper segmented by two raters showed substantial to excellent inter-rater reliability for both setMag and NM-MRI images. The DSCs of SNhyper between setMag and NM-MRI images showed substantial to excellent voxel-wise overlap in HCs (0.80 ~ 0.83) and PD (0.73 ~ 0.76), and no significant difference was found between the SNhyper volumes of setMag and NM-MRI images in either HCs or PD (p > 0.05). The mean SNhyper volume was significantly decreased in PD patients in comparison with HCs on both setMag images (77.61 mm3 vs 95.99 mm3, p < 0.0001) and NM-MRI images (79.06 mm3 vs 96.00 mm3, p < 0.0001). Areas under the curve (AUCs) of mean SNhyper volume for PD diagnosis were 0.904 on setMag and 0.906 on NM-MRI images. No significant difference was found between the two curves (p = 0.96). CONCLUSIONS: SNhyper on setMag derived from QSM demonstrated substantial spatial overlap with that on NM-MRI and provided comparable PD diagnostic performance, providing a new QSM-based multi-contrast imaging strategy for future PD studies.


Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Melaninas/análise , Doença de Parkinson/diagnóstico por imagem , Substância Negra/diagnóstico por imagem , Idoso , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Curva ROC , Reprodutibilidade dos Testes
17.
Neurology ; 95(3): e280-e290, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32616674

RESUMO

OBJECTIVE: To investigate whether the patterns of striatal dopamine depletion on dopamine transporter (DAT) scans could provide information on the long-term prognosis in Parkinson disease (PD). METHODS: We enrolled 205 drug-naive patients with early-stage PD, who underwent 18F-FP-CIT PET scans at initial assessment and received PD medications for 3 or more years. After quantifying the DAT availability in each striatal subregion, factor analysis was conducted to simplify the identification of striatal dopamine depletion patterns and to yield 4 striatal subregion factors. We assessed the effect of these factors on the development of levodopa-induced dyskinesia (LID), wearing-off, freezing of gait (FOG), and dementia during the follow-up period (6.84 ± 1.80 years). RESULTS: The 4 factors indicated which striatal subregions were relatively preserved: factor 1 (caudate), factor 2 (more-affected sensorimotor striatum), factor 3 (less-affected sensorimotor striatum), and factor 4 (anterior putamen). Cox regression analyses using the composite scores of these striatal subregion factors as covariates demonstrated that selective dopamine depletion in the sensorimotor striatum was associated with a higher risk for developing LID. Selective dopamine loss in the putamen, particularly in the anterior putamen, was associated with early development of wearing-off. Selective involvement of the anterior putamen was associated with a higher risk for dementia conversion. However, the patterns of striatal dopamine depletion did not affect the risk of FOG. CONCLUSIONS: These findings suggested that the patterns of striatal dopaminergic denervation, which were estimated by the equation derived from the factor analysis, have a prognostic implication in patients with early-stage PD.


Assuntos
Corpo Estriado/diagnóstico por imagem , Corpo Estriado/metabolismo , Dopamina/metabolismo , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/metabolismo , Tomografia por Emissão de Pósitrons/tendências , Idoso , Diagnóstico Precoce , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
18.
Clin Imaging ; 68: 94-98, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32580108

RESUMO

PURPOSE: Magnetic resonance guided focused ultrasound (MRgFUS) of the globus pallidus interna (GPi) has shown promise in the treatment of drug-resistant Parkinson's disease, though direct visualization of the GPi remains challenging with MRI. The purpose of this study was to compare various preoperative MR imaging techniques and to evaluate the utility of quantitative susceptibility imaging (QSM) in the depiction of the GPi prior to MRgFUS ablation. MATERIALS AND METHODS: Six patients with medication refractory advanced idiopathic Parkinson's disease were referred for preoperative MR imaging prior to MRgFUS pallidotomy. Axial T1WI and T2WI, Fast Gray Matter Acquisition T1 Inversion Recovery (FGATIR), and QSM sequences were acquired. DTI tractography was performed to delineate the corticospinal tracts. Qualitative visualization scores and contrast to noise ratios (CNR) were recorded and measured on all images. RESULTS: QSM had significantly higher median qualitative visualization scores (3.00) compared with the T1WI (1.00), T2WI (1.50), and FGATIR sequences (1.50) (p < 0.05). QSM provided superior CNR for GPi depiction in each category (GPi-GPe and GPi-IC), respectively. For GPi-GPe, median CNR for T1WI, T2WI, FGATIR, and QSM was 1.13, 1.68, 0.79, and 10.78. For GPi-IC, median CNR for T1WI, T2WI, FGATIR, and QSM was 1.48, 4.63, 4.24, and 40.26, respectively (p < 0.05). CONCLUSION: QSM offers improved visualization of the GPi compared with the traditional and currently recommended MR sequences prior to MRgFUS ablation in patients with Parkinson's disease. These results suggest that QSM should be considered as part of all preoperative imaging protocols prior to MRgFUS pallidotomy.


Assuntos
Doença de Parkinson , Globo Pálido/diagnóstico por imagem , Globo Pálido/cirurgia , Substância Cinzenta , Humanos , Imagem por Ressonância Magnética , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/cirurgia , Ultrassonografia
19.
Neurology ; 95(3): e291-e298, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32576636

RESUMO

OBJECTIVE: To determine whether deep white matter and periventricular hyperintensities affect the motor symptoms of Parkinson disease (PD) differently, we analyzed MRI and dopamine transporter imaging. METHODS: We analyzed the medical records of patients with de novo PD who underwent dopamine transporter PET scanning and MRI at their first visit. Deep white matter and periventricular hyperintensities were scored with a visual rating scale, and motor symptoms were assessed by Unified Parkinson's Disease Rating Scale motor score and tremor, rigidity, bradykinesia, and axial symptom subscores. The influence of white matter hyperintensity on motor symptoms was explored using multivariable linear regression models. RESULTS: A total of 93 patients (mean age, 67.2 ± 9.9 years; 44 male) were included and the mean motor score was 25.0 ± 10.8. Subscores for bradykinesia and axial symptoms were correlated with both deep white matter and periventricular hyperintensities scores. Multivariable linear regression models revealed that deep white matter hyperintensities score was significantly associated with subscore for bradykinesia and periventricular hyperintensities score was associated with subscores for bradykinesia and axial symptoms after adjusting for putaminal dopamine transporter availability and clinical factors. CONCLUSIONS: These results demonstrate that deep white matter hyperintensities are associated with bradykinesia and periventricular hyperintensities are associated with bradykinesia and axial symptoms in patients with PD independently of the severity of dopaminergic depletion.


Assuntos
Transtornos das Habilidades Motoras/diagnóstico por imagem , Transtornos das Habilidades Motoras/metabolismo , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/metabolismo , Substância Branca/diagnóstico por imagem , Substância Branca/metabolismo , Idoso , Feminino , Humanos , Imagem por Ressonância Magnética/tendências , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/tendências
20.
World Neurosurg ; 138: 672-679, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32545020

RESUMO

OBJECTIVE: In this study, we considered the treatment of cognitive characteristics of Parkinson's subtypes under resting magnetic resonance imaging scans, and used magnetic resonance imaging to analyze brain activity characteristics of patients with Parkinson's subtypes at rest. METHODS: In this study, patients with neurological Parkinson's disease subtypes were selected: 27 patients in the tremor group, 33 patients in the orthostatic gastric instability group, and 3 patients with mild cognitive impairment and neuropathic Parkinson's disease. Scientific treatment was adopted. RESULTS: Nineteen patients had mild cognitive dysfunction tremor and unstable posture, and 23 of them had mild cognitive dysfunction. Fifteen healthy controls were subjected to resting state functional magnetic resonance imaging by plane echo imaging sequence scanning. Neurological diseases-Regional consistency analysis of brain regions in patients with Parkinson's disease increased, including the right lower lobe, while regional consistency analysis of brain regions decreased, including the right frontal gyrus, right middle anterior gyrus, and lateral cerebellum. CONCLUSIONS: The experimental results show that the local consistency analysis method based on resting magnetic resonance imaging scan can effectively detect the differences in early neural activity in patients with Parkinson's disease subtype cognitive impairment, and can effectively reflect the brain characteristics of Parkinson's disease.


Assuntos
Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Doença de Parkinson/diagnóstico por imagem , Idoso , Estudos de Casos e Controles , Cognição , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/psicologia , Feminino , Neuroimagem Funcional , Transtornos Neurológicos da Marcha/fisiopatologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/fisiopatologia , Doença de Parkinson/psicologia , Descanso , Tremor/fisiopatologia
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