RESUMO
INTRODUCTION: In this research, our primary objective was to explore the correlation between basal ganglia dopaminergic neurotransmission, assessed using 123I-FP-CIT (DAT-SPECT), and finger movements abnormalities in patients with essential tremor (ET) and Parkinson's disease (PD). METHODS: We enrolled 16 patients with ET, 17 with PD, and 18 healthy controls (HC). Each participant underwent comprehensive clinical evaluations, kinematic assessments of finger tapping. ET and PD patients underwent DAT-SPECT imaging. The DAT-SPECT scans were subjected to both visual and semi-quantitative analysis using DaTQUANT®. We then investigated the correlations between the clinical, kinematic, and DAT-SPECT data, in patients. RESULTS: Our findings confirm that individuals with ET exhibited slower finger tapping than HC. Visual evaluation of radiotracer uptake in both striata demonstrated normal levels within the ET patient cohort, while PD patients displayed reduced uptake. However, there was notable heterogeneity in the quantification of uptake within the striata among ET patients. Additionally, we found a correlation between the amount of radiotracer uptake in the striatum and movement velocity during finger tapping in patients. Specifically, lower radioligand uptake corresponded to decreased movement velocity (ET: coef. = 0.53, p-adj = 0.03; PD: coef. = 0.59, p-adj = 0.01). CONCLUSION: The study's findings suggest a potential link between subtle changes in central dopaminergic tone and altered voluntary movement execution, in ET. These results provide further insights into the pathophysiology of ET. However, longitudinal studies are essential to determine whether the slight reduction in dopaminergic tone observed in ET patients represents a distinct subtype of the disease or could serve as a predictor for the clinical progression into PD.
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Tremor Essencial , Doença de Parkinson , Humanos , Tremor Essencial/diagnóstico por imagem , Hipocinesia/diagnóstico por imagem , Hipocinesia/etiologia , Doença de Parkinson/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Corpo Estriado , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismoRESUMO
BACKGROUND: Conventional MRI scans have limited usefulness in monitoring Parkinson's disease as they typically do not show any disease-specific brain abnormalities. This study aimed to identify an imaging biomarker for tracking motor symptom progression by using a multivariate statistical approach that can combine gray matter volume information from multiple brain regions into a single score specific to each PD patient. METHODS: A cohort of 150 patients underwent MRI at baseline and had their motor symptoms tracked for up to 10 years using MDS-UPDRS-III, with motor symptoms focused on total and subscores, including rigidity, bradykinesia, postural instability, and gait disturbances, resting tremor, and postural-kinetic tremor. Gray matter volume extracted from MRI data was summarized into a patient-specific summary score using Mahalanobis distance, MGMV. MDS-UPDRS-III's progression and its association with MGMV were modeled via linear mixed-effects models over 5- and 10-year follow-up periods. RESULTS: Over the 5-year follow-up, there was a significant increase (P < 0.05) in MDS-UPDRS-III total and subscores, except for postural-kinetic tremor. Over the 10-year follow-up, all MDS-UPDRS-III scores increased significantly (P < 0.05). A higher baseline MGMV was associated with a significant increase in MDS-UPDRS-III total, bradykinesia, postural instability and gait disturbances, and resting tremor (P < 0.05) over the 5-year follow-up, but only with total, bradykinesia, and postural instability and gait disturbances during the 10-year follow-up (P < 0.05). CONCLUSIONS: Higher MGMV scores were linked to faster motor symptom progression, suggesting it could be a valuable marker for clinicians monitoring Parkinson's disease over time.
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Doença de Parkinson , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Tremor/etiologia , Tremor/complicações , Hipocinesia/diagnóstico por imagem , Hipocinesia/etiologia , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância MagnéticaRESUMO
The mechanisms underlying motor fluctuations in patients with Parkinson's disease (PD) are currently unclear. Regional brain stimulation reported the changing of motor symptoms, but the correlation with functional connectivity (FC) in the brain network is not fully understood. Hence, our study aimed to explore the relationship between motor symptom severity and FC using resting-state functional magnetic resonance imaging (rsfMRI) in the "on" and "off" states of PD. In 26 patients with sporadic PD, FC was assessed using rsfMRI, and clinical severity was analyzed using the motor part of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS Part III) in the on and off states. Correlations between FC values and MDS-UPDRS Part III scores were assessed using Pearson's correlation coefficient. The correlation between FC and motor symptoms differed in the on and off states. FC between the ipsilateral precentral gyrus (PreCG) and globus pallidus (GP) correlated with the total MDS-UPDRS Part III scores and those for bradykinesia/rigidity in the off state. Lateralization analysis indicated that FC between the PreCG and GP correlated with the contralateral total MDS-UPDRS Part III scores and those for bradykinesia/rigidity in the off state. Aberrant FC in cortico-striatal circuits correlated with the severity of motor symptoms in PD. Cortico-striatal hyperconnectivity, particularly in motor pathways involving PreCG and GP, is related to motor impairments in PD. These findings may facilitate our understanding of the mechanisms underlying motor symptoms in PD and aid in developing treatment strategies such as brain stimulation for motor impairment.
Assuntos
Córtex Motor , Doença de Parkinson , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/tratamento farmacológico , Globo Pálido/diagnóstico por imagem , Córtex Motor/diagnóstico por imagem , Hipocinesia/diagnóstico por imagem , Hipocinesia/etiologia , Imageamento por Ressonância Magnética/métodosRESUMO
Dysfunctional dopaminergic neurotransmission is central to movement disorders and mental diseases. The dopamine transporter (DAT) regulates extracellular dopamine levels, but the genetic and mechanistic link between DAT function and dopamine-related pathologies is not clear. Particularly, the pathophysiological significance of monoallelic missense mutations in DAT is unknown. Here, we use clinical information, neuroimaging, and large-scale exome-sequencing data to uncover the occurrence and phenotypic spectrum of a DAT coding variant, DAT-K619N, which localizes to the critical C-terminal PSD-95/Discs-large/ZO-1 homology-binding motif of human DAT (hDAT). We identified the rare but recurrent hDAT-K619N variant in exome-sequenced samples of patients with neuropsychiatric diseases and a patient with early-onset neurodegenerative parkinsonism and comorbid neuropsychiatric disease. In cell cultures, hDAT-K619N displayed reduced uptake capacity, decreased surface expression, and accelerated turnover. Unilateral expression in mouse nigrostriatal neurons revealed differential effects of hDAT-K619N and hDAT-WT on dopamine-directed behaviors, and hDAT-K619N expression in Drosophila led to impairments in dopamine transmission with accompanying hyperlocomotion and age-dependent disturbances of the negative geotactic response. Moreover, cellular studies and viral expression of hDAT-K619N in mice demonstrated a dominant-negative effect of the hDAT-K619N mutant. Summarized, our results suggest that hDAT-K619N can effectuate dopamine dysfunction of pathological relevance in a dominant-negative manner.
Assuntos
Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Dopamina/metabolismo , Transtornos Mentais/genética , Neurônios/metabolismo , Transtornos Parkinsonianos/genética , Adulto , Animais , Comportamento Animal , Transporte Biológico , Células Cultivadas , Bases de Dados Genéticas , Drosophila , Exoma , Feminino , Humanos , Hipocinesia/diagnóstico por imagem , Hipocinesia/genética , Hipocinesia/metabolismo , Masculino , Transtornos Mentais/metabolismo , Mesencéfalo/metabolismo , Camundongos , Pessoa de Meia-Idade , Atividade Motora/genética , Mutação , Transtornos Parkinsonianos/diagnóstico por imagem , Transtornos Parkinsonianos/metabolismo , Fenótipo , Transmissão Sináptica , Tomografia Computadorizada de Emissão de Fóton Único , TransfecçãoRESUMO
BACKGROUND: We report a rare case of left ventricular inflow obstruction from a branch of the left circumflex coronary artery to the right atrium caused by a coronary arteriovenous fistula (CAVF) in a young Japanese male child. CASE PRESENTATION: The patient was diagnosed with CAVF following a heart murmur shortly after birth. The left-to-right shunt caused right ventricular volume overload and pulmonary congestion. An emergency surgical intervention was performed for the CAVF on day 6 after birth. However, by 5 years of age, his left ventricular inflow obstruction worsened. We found an abnormal blood vessel originating from the proximal part of a branch of the left circumflex coronary artery, circling the outside of the mitral valve annulus along the medial side of the coronary sinus. As the child gets older, the blood inflow into the left ventricle might get restricted further, resulting in left-sided heart failure. CONCLUSION: Our findings suggest that even after CAVF closure surgery, it is essential to monitor for complications caused by progressive dilatation of a persistent CAVF.
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Fístula Arteriovenosa/complicações , Anomalias dos Vasos Coronários/complicações , Ventrículos do Coração , Hiperemia/etiologia , Fatores Etários , Fístula Arteriovenosa/cirurgia , Pré-Escolar , Seio Coronário , Anomalias dos Vasos Coronários/cirurgia , Dilatação Patológica/complicações , Humanos , Hipocinesia/diagnóstico por imagem , Recém-Nascido , Masculino , Valva Mitral , Veias Pulmonares , Disfunção Ventricular Esquerda/diagnóstico por imagemAssuntos
Humanos , Feminino , Adulto , Síndrome Antifosfolipídica/diagnóstico por imagem , Hipocinesia/diagnóstico por imagem , Síndrome Coronariana Aguda/terapia , Síndrome Coronariana Aguda/diagnóstico por imagem , Artéria Coronária Esquerda Anormal/patologia , Dor no Peito , Ecocardiografia/métodos , Cateterismo Cardíaco/métodos , Heparina/química , Enoxaparina/química , Eletrocardiografia/métodos , Angiografia por Tomografia Computadorizada/métodos , Anticoagulantes/químicaAssuntos
Betacoronavirus , Cardiologistas/psicologia , Dor no Peito/etiologia , Infecções por Coronavirus/diagnóstico , Traumatismos Cardíacos/diagnóstico por imagem , Pneumonia Viral/diagnóstico , Adulto , COVID-19 , Teste para COVID-19 , Dor no Peito/diagnóstico por imagem , Técnicas de Laboratório Clínico , Infecções por Coronavirus/epidemiologia , Traumatismos Cardíacos/complicações , Humanos , Hipocinesia/diagnóstico por imagem , Masculino , Pandemias , Pneumonia Viral/epidemiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2 , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To report a case of a patient infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who acutely developed a hypokinetic-rigid syndrome. METHODS: Patient data were obtained from medical records from the Hospital Universitario 12 de Octubre in Madrid, Spain. [123I]-ioflupane dopamine transporter (DaT) SPECT images were acquired 4 hours after a single dose of 185 MBq of 123I-FP-CIT. Quantitative analysis was performed with DaTQUANT software providing the specific binding ratio and z score values of the striatum. RESULTS: We report a previously healthy 58-year-old man who developed hyposmia, generalized myoclonus, fluctuating and transient changes in level of consciousness, opsoclonus, and an asymmetric hypokinetic-rigid syndrome with ocular abnormalities after a severe SARS-CoV-2 infection. DaT-SPECT confirmed a bilateral decrease in presynaptic dopamine uptake asymmetrically involving both putamina. Significant improvement in the parkinsonian symptoms was observed without any specific treatment. CONCLUSION: This case study provides clinical and functional neuroimaging evidence to support that SARS-CoV-2 can gain access to the CNS, affecting midbrain structures and leading to neurologic signs and symptoms.
Assuntos
Infecções por Coronavirus/fisiopatologia , Doença de Parkinson Pós-Encefalítica/fisiopatologia , Pneumonia Viral/fisiopatologia , Putamen/diagnóstico por imagem , Betacoronavirus , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , COVID-19 , Transtornos da Consciência , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico por imagem , Progressão da Doença , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Eletroencefalografia , Humanos , Hipocinesia/diagnóstico por imagem , Hipocinesia/etiologia , Hipocinesia/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rigidez Muscular/diagnóstico por imagem , Rigidez Muscular/etiologia , Rigidez Muscular/fisiopatologia , Nortropanos , Transtornos da Motilidade Ocular , Pandemias , Doença de Parkinson Pós-Encefalítica/diagnóstico por imagem , Doença de Parkinson Pós-Encefalítica/etiologia , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico por imagem , Putamen/metabolismo , SARS-CoV-2 , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
The age at onset (AAO) is an important determinant in Parkinson's disease (PD). Neuroimaging genetics is suitable for studying AAO in PD as it jointly analyzes imaging and genetics. We aimed to identify features associated with AAO in PD by applying the objective-specific neuroimaging genetics approach and constructing an AAO prediction model. Our objective-specific neuroimaging genetics extended the sparse canonical correlation analysis by an additional data type related to the target task to investigate possible associations of the imaging-genetic, genetic-target, and imaging-target pairs simultaneously. The identified imaging, genetic, and combined features were used to construct analytical models to predict the AAO in a nested five-fold cross-validation. We compared our approach with those from two feature selection approaches where only associations of imaging-target and genetic-target were explored. Using only imaging features, AAO prediction was accurate in all methods. Using only genetic features, the results from other methods were worse or unstable compared to our model. Using both imaging and genetic features, our proposed model predicted the AAO well (r = 0.5486). Our findings could have significant impacts on the characterization of prodromal PD and contribute to diagnosing PD early because genetic features could be measured accurately from birth.
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Genética Médica/estatística & dados numéricos , Modelos Estatísticos , Neuroimagem/estatística & dados numéricos , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/genética , Sintomas Prodrômicos , Idade de Início , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/patologia , Feminino , Loci Gênicos , Genética Médica/métodos , Humanos , Hipocinesia/diagnóstico por imagem , Hipocinesia/genética , Hipocinesia/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodos , Doença de Parkinson/patologia , Polimorfismo de Nucleotídeo Único , Prognóstico , Estudos Retrospectivos , Tremor/diagnóstico por imagem , Tremor/genética , Tremor/patologiaRESUMO
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/fisiopatologiaRESUMO
BACKGROUND: Up to 90% of patients with Parkinson's disease (PD) eventually develop the speech and voice disorder referred to as hypokinetic dysarthria (HD). However, the brain morphological changes associated with HD have not been investigated. Moreover, no reliable model for predicting the severity of HD based on neuroimaging has yet been developed. METHODS: A total of 134 PD patients were included in this study and divided into a training set and a test set. All participants underwent a structural magnetic resonance imaging (MRI) scan and neuropsychological evaluation. Individual cortical thickness, subcortical structure, and white matter volume were extracted, and their association with HD severity was analyzed. After feature selection, a machine-learning model was established using a support vector machine in the training set. The severity of HD was then predicted in the test set. RESULTS: Atrophy of the right precentral cortex and the right fusiform gyrus was significantly associated with HD. No association was found between HD and volume of white matter or subcortical structures. Favorable and optimal performance of machine learning on HD severity prediction was achieved using feature selection, giving a correlation coefficient (r) of .7516 and a coefficient of determination (R2 ) of .5649 (P < .001). CONCLUSION: The brain morphological changes were associated with HD. Excellent prediction of the severity of HD was achieved using machine learning based on neuroimaging.
Assuntos
Encéfalo/diagnóstico por imagem , Disartria/diagnóstico por imagem , Hipocinesia/diagnóstico por imagem , Aprendizado de Máquina , Doença de Parkinson/diagnóstico por imagem , Índice de Gravidade de Doença , Idoso , Disartria/epidemiologia , Feminino , Humanos , Hipocinesia/epidemiologia , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/epidemiologia , Valor Preditivo dos Testes , Estudos RetrospectivosRESUMO
BACKGROUND: Acute water intoxication after hysteroscopy is a rare, life-threatening condition, often accompanied with delayed diagnosis owing to masked symptoms because of general anesthesia. CASE PRESENTATION: Herein we presented a 39-year-old female who presented with cardiac arrest after hysteroscopic myomectomy because of acute water intoxication and survived after extracorporeal membrane oxygenation, continuous venous-venous hemofiltration, and aggressive high sodium fluid resuscitation. CONCLUSION: Failure to recognize and treat this condition appropriately may lead to potentially lethal cardiopulmonary complications.
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Oxigenação por Membrana Extracorpórea , Parada Cardíaca/etiologia , Hipocinesia/diagnóstico por imagem , Complicações Intraoperatórias , Edema Pulmonar/diagnóstico por imagem , Irrigação Terapêutica/efeitos adversos , Miomectomia Uterina/efeitos adversos , Neoplasias Uterinas/cirurgia , Intoxicação por Água/complicações , Adulto , Terapia de Substituição Renal Contínua/métodos , Ecocardiografia , Feminino , Humanos , Histeroscopia , Gravidez , Tomografia Computadorizada por Raios X , Água , Intoxicação por Água/terapiaRESUMO
No disponible
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Humanos , Feminino , Pessoa de Meia-Idade , Cardiomiopatia de Takotsubo/diagnóstico por imagem , Cardiomiopatia de Takotsubo/terapia , Hipocinesia/diagnóstico por imagem , Oclusão Coronária/diagnóstico por imagem , Ecocardiografia/métodos , Radiografia Torácica , Edema Pulmonar/diagnóstico por imagem , Imagem de Perfusão do MiocárdioRESUMO
BACKGROUND: The selection of optimal deep brain stimulation (DBS) parameters is time-consuming, experience-dependent, and best suited when acute effects of stimulation can be observed (e.g., tremor reduction). OBJECTIVES: To test the hypothesis that optimal stimulation location can be estimated based on the cortical connections of DBS contacts. METHODS: We analyzed a cohort of 38 patients with Parkinson's disease (24 training, and 14 test cohort). Using whole-brain probabilistic tractography, we first mapped the cortical regions associated with stimulation-induced efficacy (rigidity, bradykinesia, and tremor improvement) and side effects (paresthesia, motor contractions, and visual disturbances). We then trained a support vector machine classifier to categorize DBS contacts into efficacious, defined by a therapeutic window ≥2 V (threshold for side effect minus threshold for efficacy), based on their connections with cortical regions associated with efficacy versus side effects. The connectivity-based classifications were then compared with actual stimulation contacts using receiver-operating characteristics (ROC) curves. RESULTS: Unique cortical clusters were associated with stimulation-induced efficacy and side effects. In the training dataset, 42 of the 47 stimulation contacts were accurately classified as efficacious, with a therapeutic window of ≥3 V in 31 (66%) and between 2 and 2.9 V in 11 (24%) electrodes. This connectivity-based estimation was successfully replicated in the test cohort with similar accuracy (area under ROC = 0.83). CONCLUSIONS: Cortical connections can predict the efficacy of DBS contacts and potentially facilitate DBS programming. The clinical utility of this paradigm in optimizing DBS outcomes should be prospectively tested, especially for directional electrodes.
Assuntos
Estimulação Encefálica Profunda/métodos , Doença de Parkinson/terapia , Idoso , Encéfalo/diagnóstico por imagem , Estimulação Encefálica Profunda/efeitos adversos , Estudos de Viabilidade , Humanos , Hipocinesia/diagnóstico por imagem , Hipocinesia/terapia , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico por imagem , Tremor/diagnóstico por imagem , Tremor/terapiaRESUMO
OBJECTIVE: Subthalamic deep brain stimulation may alleviate bradykinesia in Parkinson patients. Research suggests that this stimulation effect may be mediated by brain networks like the corticocerebellar loop. This study investigated the connectivity between stimulation sites and cortical and subcortical structures to identify connections for effective stimulation. METHODS: We retrospectively investigated 21 patients with Parkinson disease with bilateral subthalamic deep brain stimulation. Stimulation effectiveness in reducing bradykinesia, tremor, and rigidity was evaluated for each electrode contact in brain hemispheres contralateral to the affected hemibody. Dysarthric side effects were also examined. Probabilistic tractography based on diffusion-weighted imaging was performed in individual patient-specific brains using electrode contacts as seeds. Connectivity profiles of contacts with effective and noneffective stimulation were compared. RESULTS: Connectivity profiles of effective and noneffective contacts differed. Moreover, the connectivity profile for bradykinesia differed from that for rigidity, tremor, or dysarthria. Regarding bradykinesia, effective contacts were significantly more often connected with the ipsilateral superior cerebellar peduncle and the ipsilateral dentate nucleus, which correspond to the ipsilateral portion of the cerebellothalamocortical pathway. Rigidity was mitigated by stimulation of ascending brainstem and intralaminar thalamic connections. Tremor alleviation was related to connections with the internal capsule (anterior limb) and the pallidum. Dysarthric side effects were associated with connections to the supplementary motor area and the decussating cerebellothalamocortical pathway. INTERPRETATION: Whereas bradykinesia seems to be mitigated by stimulation of the ascending, ipsilateral cerebellothalamocortical pathway, stimulation of the descending corticopontocerebellar pathway may be ineffective. Rigidity, tremor, and dysarthric side effects seem to be influenced by different neural networks. ANN NEUROL 2019;85:852-864.
Assuntos
Estimulação Encefálica Profunda/métodos , Hipocinesia/diagnóstico por imagem , Hipocinesia/terapia , Rede Nervosa/diagnóstico por imagem , Núcleo Subtalâmico/diagnóstico por imagem , Idoso , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/fisiologia , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/terapia , Estudos Retrospectivos , Núcleo Subtalâmico/fisiologiaRESUMO
Parkinson's disease causes a characteristic combination of motor symptoms due to progressive neurodegeneration of dopaminergic neurons in the substantia nigra pars compacta. The core impairment of dopaminergic neurotransmission has motivated the use of functional magnetic resonance imaging (fMRI) in patients with Parkinson's disease to elucidate the role of dopamine in motor control and cognition in humans. Here we review the main insights from functional brain imaging in Parkinson's disease. Task-related fMRI revealed many disease-related alterations in brain activation patterns. However, the interpretation of these findings is complicated by the fact that task-dependent activity is influenced by complex interactions between the amount of dopaminergic neurodegeneration in the task-relevant nuclei, the state of medication, genetic factors and performance. Despite these ambiguities, fMRI studies in Parkinson's disease demonstrated a central role of dopamine in the generation of movement vigour (bradykinesia) and the control of excessive movements (dyskinesia), involving changes of both activity and connectivity of the putamen, premotor and motor regions, and right inferior frontal gyrus (rIFG). The fMRI studies addressing cognitive flexibility provided convergent evidence for a non-linear, U-shaped, relationship between dopamine levels and performance. The amount of neurodegeneration in the task-relevant dopaminergic nuclei and pharmacological dopamine replacement can therefore move performance either away or towards the task-specific optimum. Dopamine levels also strongly affect processing of reward and punishment for optimal learning. However, further studies are needed for a detailed understanding of the mechanisms underlying these effects.
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Disfunção Cognitiva , Dopamina/fisiologia , Função Executiva/fisiologia , Hipercinese , Hipocinesia , Neuroimagem , Doença de Parkinson , Recompensa , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Humanos , Hipercinese/diagnóstico por imagem , Hipercinese/etiologia , Hipercinese/metabolismo , Hipercinese/fisiopatologia , Hipocinesia/diagnóstico por imagem , Hipocinesia/etiologia , Hipocinesia/metabolismo , Hipocinesia/fisiopatologia , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/metabolismo , Doença de Parkinson/fisiopatologiaAssuntos
Tosse/fisiopatologia , Síndrome Hipereosinofílica/fisiopatologia , Pólipos Nasais/fisiopatologia , Rinite Alérgica/fisiopatologia , Trombofilia/fisiopatologia , Idoso , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Artralgia/diagnóstico por imagem , Artralgia/tratamento farmacológico , Artralgia/imunologia , Artralgia/fisiopatologia , Doença Crônica , Síndrome de Churg-Strauss/diagnóstico por imagem , Síndrome de Churg-Strauss/tratamento farmacológico , Síndrome de Churg-Strauss/imunologia , Síndrome de Churg-Strauss/fisiopatologia , Tosse/diagnóstico por imagem , Tosse/tratamento farmacológico , Tosse/imunologia , Diagnóstico Diferencial , Eosinófilos/efeitos dos fármacos , Eosinófilos/imunologia , Eosinófilos/patologia , Humanos , Síndrome Hipereosinofílica/diagnóstico por imagem , Síndrome Hipereosinofílica/tratamento farmacológico , Síndrome Hipereosinofílica/imunologia , Hipocinesia/diagnóstico por imagem , Hipocinesia/tratamento farmacológico , Hipocinesia/imunologia , Hipocinesia/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Hemissuccinato de Metilprednisolona/uso terapêutico , Pólipos Nasais/diagnóstico por imagem , Pólipos Nasais/tratamento farmacológico , Pólipos Nasais/imunologia , Prednisona/uso terapêutico , Rinite Alérgica/diagnóstico por imagem , Rinite Alérgica/tratamento farmacológico , Rinite Alérgica/imunologia , Trombofilia/diagnóstico por imagem , Trombofilia/tratamento farmacológico , Trombofilia/imunologia , Resultado do TratamentoRESUMO
Classical motor symptoms of Parkinson's disease (PD) such as tremor, rigidity, bradykinesia, and axial symptoms are graded in the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III. It is yet to be ascertained whether parkinsonian motor symptoms are associated with different anatomical patterns of neurodegeneration as reflected by brain grey matter (GM) alteration. This study aimed to investigate associations between motor subscores and brain GM at voxel level. High resolution structural MRI T1 scans from the Parkinson's Progression Markers Initiative (PPMI) repository were employed to estimate brain GM intensity of PD subjects. Correlations between GM intensity and total MDS-UPDRS III and its four subscores were computed. The total MDS-UPDRS III score was significantly negatively correlated bilaterally with putamen and caudate GM density. Lower anterior striatal GM intensity was significantly associated with higher rigidity subscores, whereas left-sided anterior striatal and precentral cortical GM reduction were correlated with severity of axial symptoms. No significant morphometric associations were demonstrated for tremor subscores. In conclusion, we provide evidence for neuroanatomical patterns underpinning motor symptoms in early PD.
Assuntos
Encéfalo/patologia , Substância Cinzenta/patologia , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/patologia , Idoso , Feminino , Humanos , Hipocinesia/diagnóstico por imagem , Hipocinesia/patologia , Interpretação de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rigidez Muscular/diagnóstico por imagem , Rigidez Muscular/patologia , Tremor/diagnóstico por imagem , Tremor/patologiaRESUMO
Importance: Brain hypometabolism is associated with the clinical consequences of the degenerative process, but little is known about regional hypermetabolism, sometimes observed in the brain of patients with clinically manifest Huntington disease (HD). Studying the role of regional hypermetabolism is needed to better understand its interaction with the motor symptoms of the disease. Objective: To investigate the association between brain hypometabolism and hypermetabolism with motor scores of patients with early HD. Design, Setting, and Participants: This study started in 2001, and analysis was completed in 2016. Sixty symptomatic patients with HD and 15 healthy age-matched control individuals underwent positron emission tomography to measure cerebral metabolism in this cross-sectional study. They also underwent the Unified Huntington's Disease Rating Scale motor test, and 2 subscores were extracted: (1) a hyperkinetic score, combining dystonia and chorea, and (2) a hypokinetic score, combining bradykinesia and rigidity. Main Outcomes and Measures: Statistical parametric mapping software (SPM5) was used to identify all hypo- and hypermetabolic regions in patients with HD relative to control individuals. Correlation analyses (P < .001, uncorrected) between motor subscores and brain metabolic values were performed for regions with significant hypometabolism and hypermetabolism. Results: Among 60 patients with HD, 22 were women (36.7%), and the mean (SD) age was 44.6 (7.6) years. Of the 15 control individuals, 7 were women (46.7%), and the mean (SD) age was 42.2 (7.3) years. In statistical parametric mapping, striatal hypometabolism was significantly correlated with the severity of all motor scores. Hypermetabolism was negatively correlated only with hypokinetic scores in the cuneus (z score = 3.95, P < .001), the lingual gyrus (z score = 4.31, P < .001), and the crus I/II of the cerebellum (z score = 3.77, P < .001), a region connected to associative cortical areas. More severe motor scores were associated with higher metabolic values in the inferior parietal lobule, anterior cingulate, inferior temporal lobule, the dentate nucleus, and the cerebellar lobules IV/V, VI, and VIII bilaterally corresponding to the motor regions of the cerebellum (z score = 3.96 and 3.42 in right and left sides, respectively; P < .001). Conclusions and Relevance: Striatal hypometabolism is associated with clinical disease severity. Conversely, hypermetabolism is likely compensatory in regions where it is associated with decreasing motor scores. Hypermetabolism might be detrimental in other structures in which it is associated with more severe motor symptoms. In the cerebellum, both compensatory and detrimental contributions seem to occur. This study helps to better understand the motor clinical relevance of hypermetabolic brain regions in HD.