RESUMO
BACKGROUND AND PURPOSE: To determine whether iron deposition in deep brain nuclei assessed using high-pass filtered phase imaging plays a role in motor disease severity in Parkinson's disease (PD). METHODS: Seventy patients with mild to moderate PD and 20 age- and gender-matched healthy volunteers (HVs) underwent susceptibility-weighted imaging on a 3 T magnetic resonance imaging scanner. Phase shifts (radians) in deep brain nuclei were derived from high-pass filtered phase images and compared between groups. Analysis of clinical laterality and correlations with motor severity (Unified Parkinson's Disease Rating Scale, Part III, UPDRS-III) were performed. Phase shifts (in radians) were compared between HVs and three PD subgroups divided according to UPDRS-III scores using analysis of covariance, adjusting for age and regional area. RESULTS: Parkinson's disease patients had significantly (P < 0.001) higher radians than HVs bilaterally in the putamen, globus pallidus and substantia nigra (SN). The SN contralateral to the most affected side showed higher radians (P < 0.001) compared to the less affected side. SN radians positively correlated with UPDRS-III and bradykinesia-rigidity subscores, but not with tremor subscores. ancova followed by post hoc Bonferroni-adjusted pairwise comparisons revealed that SN radians were significantly greater in the PD subgroup with higher UPDRS-III scores compared to both lowest UPDRS-III PD and HV groups (P < 0.001). CONCLUSIONS: Increased nigral iron accumulation in PD appears to be stratified according to disease motor severity and correlates with symptoms related to dopaminergic neurodegeneration. This semi-quantitative in vivo iron assessment could prove useful for objectively monitoring PD progression, especially in clinical trials concerning iron chelation therapies.
Assuntos
Substância Cinzenta/metabolismo , Ferro/metabolismo , Transtornos dos Movimentos/fisiopatologia , Doença de Parkinson/metabolismo , Doença de Parkinson/fisiopatologia , Adulto , Idoso , Estudos Transversais , Suscetibilidade a Doenças , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Hipocinesia/etiologia , Hipocinesia/fisiopatologia , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transtornos dos Movimentos/etiologia , Rigidez Muscular/etiologia , Rigidez Muscular/fisiopatologia , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Substância Negra/diagnóstico por imagem , Substância Negra/metabolismoRESUMO
Levodopa-induced dyskinesias (LIDs) and graft-induced dyskinesias (GIDs) are serious and common complications of Parkinson's disease (PD) management following chronic treatment with levodopa or intrastriatal transplantation with dopamine-rich foetal ventral mesencephalic tissue, respectively. Positron emission tomography (PET) molecular imaging provides a powerful in vivo tool that has been employed over the past 20 years for the elucidation of mechanisms underlying the development of LIDs and GIDs in PD patients. PET used together with radioligands tagging molecular targets has allowed the functional investigation of several systems in the brain including the dopaminergic, serotonergic, glutamatergic, opioid, endocannabinoid, noradrenergic and cholinergic systems. In this article the role of PET imaging in unveiling pathophysiological mechanisms underlying the development of LIDs and GIDs in PD patients is reviewed.
Assuntos
Discinesia Induzida por Medicamentos/diagnóstico por imagem , Discinesia Induzida por Medicamentos/etiologia , Tomografia por Emissão de Pósitrons , Antiparkinsonianos/efeitos adversos , Fluordesoxiglucose F18 , Humanos , Levodopa/efeitos adversos , Doença de Parkinson/tratamento farmacológicoRESUMO
Buspirone is an anxiolytic drug and is a partial agonist for the serotonin 5-HT(1A) receptors as well as possessing low affinity and is an antagonist for the dopamine D(2) autoreceptors, with some evidence of a weak affinity to 5-HT(2) receptors. The underlying mechanism of action of buspirone is not clear; however it is thought that its main pharmacology is mediated via the 5-HT(1A) receptors. Initially developed for use in the treatment of generalised anxiety disorder, it appears that buspirone may be useful in various other neurological and psychiatric disorders, such as attenuating side effects of Parkinson's disease therapy, ataxia, depression, social phobia, and behaviour disturbances following brain injury, and those accompanying Alzheimer's disease, dementia and attention deficit disorder. Considering the potential of this drug to be included in the management of many conditions, thorough and controlled studies are required to elucidate the exact mechanism of action. This review will consider the evidence so far for both the potential underlying mechanisms and its use in various conditions.
Assuntos
Buspirona/farmacocinética , Buspirona/uso terapêutico , Antagonistas dos Receptores de Dopamina D2 , Agonistas do Receptor 5-HT1 de Serotonina/farmacocinética , Agonistas do Receptor 5-HT1 de Serotonina/uso terapêutico , Animais , Discinesia Induzida por Medicamentos/tratamento farmacológico , Discinesia Induzida por Medicamentos/metabolismo , Humanos , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/metabolismo , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Receptores de Dopamina D2/metabolismoRESUMO
BACKGROUND: Depression associated with Parkinson disease (PD) has a different symptom profile to endogenous depression. The etiology of depression in PD remains uncertain though abnormal serotonergic neurotransmission could play a role. OBJECTIVE: To assess with PET serotonergic function via in vivo serotonin transporter (5-HTT) availability in antidepressant-naive patients with PD. METHODS: Thirty-four patients with PD and 10 healthy matched control subjects had a clinical battery of tests including the patient-report Beck Depression Inventory-II (BDI-II), the clinician-report Hamilton Rating Scale for Depression (HRSD), and the structured clinical interview for DSM-IV Axis I Disorders (SCID-I). They underwent ¹¹C-DASB PET, a selective in vivo marker of 5-HTT binding in humans. RESULTS: BDI-II scores correlated with HRSD scores. Ten of 34 patients with PD (29.4%) had BDI-II and HRSD scores above the discriminative cutoff for PD depression though only half of these patients could be classed on SCID-I criteria as having an anxiety/mood disorder. Patients with PD with the highest scores for depression symptoms showed significantly raised ¹¹C-DASB binding in amygdala, hypothalamus, caudal raphe nuclei, and posterior cingulate cortex compared to low score cases, while ¹¹C-DASB binding values in other regions were similarly decreased in depressed and nondepressed patients with PD compared to healthy controls. CONCLUSION: Depressive symptoms in antidepressant-naive patients with PD correlate with relatively higher 5-HTT binding in raphe nuclei and limbic structures possibly reflecting lower extracellular serotonin levels. Our data are compatible with a key role of abnormal serotonergic neurotransmission contributing to the pathophysiology of PD depression and justify the use of agents acting on 5-HTT.