25 research outputs found

    The Contribution of Neuroimaging to the Understanding of Essential Tremor Pathophysiology: a Systematic Review

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    Essential tremor (ET) is one of the most common movement disorders. Over the last 10 years, magnetic resonance imaging (MRI) has shed light on the structural and functional abnormalities possibly involved in ET pathophysiology. In this systematic review, we aimed to identify the cortical and subcortical structures involved and the role that different brain areas play in the pathophysiology of motor and non-motor ET features. We found that structural (grey and white matter) cerebellar damage and connectivity alterations between the cerebellum and various cortical areas play a role in both motor and non-motor symptoms of ET. In particular, many studies found an association between MRI findings and non-motor symptoms

    Common and rare variants in TMEM175 gene concur to the pathogenesis of Parkinson’s Disease in Italian patients

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    Parkinson’s disease (PD) represents the most common neurodegenerative movement disorder. We recently identified 16 novel genes associated with PD. In this study, we focused the attention on the common and rare variants identified in the lysosomal K+ channel TMEM175. The study includes a detailed clinical and genetic analysis of 400 cases and 300 controls. Molecular studies were performed on patient-derived fibroblasts. The functional properties of the mutant channels were assessed by patch-clamp technique and co-immunoprecipitation. We have found that TMEM175 was highly expressed in dopaminergic neurons of the substantia nigra pars compacta and in microglia of the cerebral cortex of the human brain. Four common variants were associated with PD, including two novel variants rs2290402 (c.-10C > T) and rs80114247 (c.T1022C, p.M341T), located in the Kozak consensus sequence and TM3II domain, respectively. We also disclosed 13 novel highly penetrant detrimental mutations in the TMEM175 gene associated with PD. At least nine of these mutations (p.R35C, p. R183X, p.A270T, p.P308L, p.S348L, p. L405V, p.R414W, p.P427fs, p.R481W) may be sufficient to cause the disease, and the presence of mutations of other genes correlated with an earlier disease onset. In vitro functional analysis of the ion channel encoded by the mutated TMEM175 gene revealed a loss of the K+ conductance and a reduced channel affinity for Akt. Moreover, we observed an impaired autophagic/lysosomal proteolytic flux and an increase expression of unfolded protein response markers in patient-derived fibroblasts. These data suggest that mutations in TMEM175 gene may contribute to the pathophysiology of PD

    Iron metabolism and its detection through MRI in parkinsonian disorders: a systematic review

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    Iron deposition in the brain normally increase with age, but its accumulation in certain regions is ob- served in a number of neurodegenerative diseases in- cluding Parkinson’s disease (PD) and other parkinson- isms. Whether iron overload leads to dopaminergic neu- ronal death in the SN of PD patients or is instead sim- ply a by-product of the neurodegenerative progression is still yet to be ascertained. Magnetic resonance imaging (MRI) is a non-invasive method to assess brain iron content in PD patients. In PD, accurate radiologic visu- alization of basal ganglia is required. Deep gray matter nuclei are well presented in T2- and T2*-weighted im- ages. T2*-weighted gradient-echo (GRE) is widely used to assess calcifications and also for iron detection. On the other hand, new methods specifically designed for detecting iron-induced susceptibility differences can be further improved by sequences like susceptibility- weighted imaging (SWI). In the present review, we aim to summarize the available data on brain iron de- position in PD

    D-Aspartate activates mGlu receptors coupled to polyphosphoinositide hydrolysis in neonate rat brain slices

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    The n-amino acid, n-aspartate, is abundant in the developing brain, yet its function is unknown. Addition of n-aspartate to hippocampal or cortical slices prepared from 8- to 9-day-old rats stimulated polyphosphoinositide (PI) hydrolysis to a slightly greater extent than L-glutamate. The action of n-aspartate was concentration-dependent with an apparent EC(50) value of 1 mM and a maximal stimulation of 6- and 20-fold in cortical and hippocampal slices, respectively. Stimulation of PI hydrolysis by D-aspartate was largely reduced by pharmacological blockade of mGlu5 metabotropic glutamate receptors with 2-methyl-6-(phenylethynyl)pyridine. These findings suggest that p-aspartate behaves as an endogenous agonist of mGlu5 receptors during early postnatal life. (c) 2010 Elsevier Ireland Ltd. All rights reserved

    Poor self-awareness of levodopa-induced dyskinesias in Parkinson's disease: Clinical features and mechanisms

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    Objectives: To study the factors and possible mechanisms associated with decreased self-awareness of levodopa-induced dyskinesias (LIDs) in patients with Parkinson's disease (PD). Methods: We enrolled 30 PD patients with LIDs. Patients were video-recorded in an "on" phase while experiencing LIDs. LIDs were objectively rated by means of the Unified Dyskinesias Rating Scale (UDyRS) by two movement disorders specialists while examining the patients. Patients were asked to rate the body site and the severity of their LIDs according to the 5-point UDyRS. Patients then rated their own LIDs while watching the video recording of themselves. Lastly, the patients rated the LIDs of other reference PD patients on a video recording. The same reference video recordings were shown to 15 healthy individuals matched for age, gender and education. Results: Seven of the 30 PD patients investigated were subjectively unaware of the presence of their LIDs. The majority of patients, however, recognized their LIDs when watching video recording of themselves. Patients displayed a specific poor self-awareness of trunk LIDs, in both the subjective evaluation and in the video recording-based subjective evaluation. By contrast PD patients correctly recognized LIDs in video recordings of reference PD patients. Poor self-awareness correlated with predominance of motor symptoms on the left body side. Conclusions: Poor self-awareness of LIDs is present in a proportion of PD patients as a form of anosognosia. The poor self-awareness of LIDs in the trunk is likely to be due to a complex interplay involving both anosognosic mechanisms and deficits in proprioceptive axial kinesthesia. (C) 2013 Published by Elsevier Ltd
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