Publications
280 results found
Roussakis A-A, Politis M, Towey D, et al., 2015, SEROTONIN-TO-DOPAMINE TRANSPORTER RATIOS IN THE STRIATUM OF PATIENTS WITH PARKINSON'S DISEASE: IMPACT ON LEVODOPA-INDUCED DYSKINESIAS, Annual Meeting of the Association-of-British-Neurologists (ABN), Publisher: BMJ PUBLISHING GROUP, ISSN: 0022-3050
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- Citations: 1
Politis M, Lahiri N, Niccolini F, et al., 2015, Increased central microglial activation associated with peripheral cytokine levels in premanifest Huntington's disease gene carriers, NEUROBIOLOGY OF DISEASE, Vol: 83, Pages: 115-121, ISSN: 0969-9961
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- Citations: 97
Loane C, Wu K, O'Sullivan SS, et al., 2015, Psychogenic and neural visual-cue response in PD dopamine dysregulation syndrome, PARKINSONISM & RELATED DISORDERS, Vol: 21, Pages: 1336-1341, ISSN: 1353-8020
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- Citations: 10
Martin-Bastida A, Politis M, Loane C, et al., 2015, Susceptibility weighted imaging to detect nigral iron accumulation in Parkinson's disease, Annual Meeting of the Association-of-British-Neurologists (ABN), Publisher: BMJ PUBLISHING GROUP, Pages: 49-49, ISSN: 0022-3050
Introduction: Dopaminergic neuron loss in substantia nigra (SN) in patients with PD is associated with deposits of iron. Susceptibility weighted imaging (SWI) is a high-resolution MR-based imaging technique for quantifying iron depositions in vivo. SWI may be a robust biomarker for clinical characterization of PD.Methods: Forty-two patients with PD were studied with SWI imaging. Average phase shift (radians) and percentage iron deposition of the SN were analysed using SPIN software. SWI data were also compared between PD patients with early (4.0±0.5 PD duration) vs. established PD (7.7±1.9), and according to low (21.2±4.5) vs. high (41.3±8.7) UPDRS-III-assessed motor symptoms severity. Data were interrogated using analysis of covariance (age), relative to healthy controls, and using post hoc univariate tests.Results: PD patients had higher phase shift values (p<0.01) and iron deposition percentage (p<0.001) in the SN bilaterally, compared to healthy controls. Phase shift values were significantly higher in patients with established PD compared to those with early PD (p<0.05) and higher UPDRS-III motor scores (p<0.05).Conclusions: PD patients show higher levels of deposits of iron in SN compared to healthy controls, and increased iron levels in SN are associated with prolonged disease and increased motor disability
Reilmann R, Tabrizi S, Leavitt B, et al., 2015, Rationale and Design for LEGATO-HD Study: A Multinational, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Laquinimod (0.5, 1.0, and 1.5 mg/day) as Treatment in Patients with Huntington Disease., Ninth Annual Huntington Disease Clinical Research Symposium, Publisher: Springer Verlag (Germany), Pages: 246-247, ISSN: 1933-7213
Colasanti A, Guo Q, Giannetti P, et al., 2015, Hippocampal inflammation and depression in multiple sclerosis: integrating evidence from TSPO PET and resting state fMRI, 31st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Publisher: SAGE Publications (UK and US), Pages: 492-493, ISSN: 1477-0970
Niccolini F, Foltynie T, Marques TR, et al., 2015, Loss of phosphodiesterase 10A expression is associated with progression and severity in Parkinson's disease, Brain, Vol: 138, Pages: 3003-3015, ISSN: 1460-2156
The mechanisms underlying neurodegeneration and loss of dopaminergic signalling in Parkinson’s disease are still only partially understood. Phosphodiesterase 10A (PDE10A) is a basal ganglia expressed dual substrate enzyme, which regulates cAMP and cGMP signalling cascades, thus having a key role in the regulation of dopaminergic signalling in striatal pathways, and in promoting neuronal survival. This study aimed to assess in vivo the availability of PDE10A in patients with Parkinson’s disease using positron emission tomography molecular imaging with 11C-IMA107, a highly selective PDE10A radioligand. We studied 24 patients with levodopa-treated, moderate to advanced Parkinson’s disease. Their positron emission tomography imaging data were compared to those from a group of 12 healthy controls. Parametric images of 11C-IMA107 binding potential relative to non-displaceable binding (BPND) were generated from the dynamic 11C-IMA107 scans using the simplified reference tissue model with the cerebellum as the reference tissue. Corresponding region of interest analysis showed lower mean 11C-IMA107 BPND in the caudate (P < 0.001), putamen (P < 0.001) and globus pallidus (P = 0.025) in patients with Parkinson’s disease compared to healthy controls, which was confirmed with voxel-based analysis. Longer Parkinson’s duration correlated with lower 11C-IMA107 BPND in the caudate (r = −0.65; P = 0.005), putamen (r = −0.51; P = 0.025), and globus pallidus (r = −0.47; P = 0.030). Higher Unified Parkinson’s Disease Rating Scale part-III motor scores correlated with lower 11C-IMA107 BPND in the caudate (r = −0.54; P = 0.011), putamen (r = −0.48; P = 0.022), and globus pallidus (r = −0.70; P < 0.001). Higher Unified Dyskinesia Rating Scale scores in those Parkinson’s disease with levodopa-induced dyskinesias (n = 12), correlated with lower 11C-IMA107 BPND in the caudate (r = −0.73; P = 0.031) an
Niccolini F, Haider S, Reis Marques T, et al., 2015, Altered PDE10A expression detectable early before symptomatic onset in Huntington's disease., Brain, Vol: 138, Pages: 3016-3029, ISSN: 0006-8950
There is an urgent need for early biomarkers and novel disease-modifying therapies in Huntington's disease. Huntington's disease pathology involves the toxic effect of mutant huntingtin primarily in striatal medium spiny neurons, which highly express phosphodiesterase 10A (PDE10A). PDE10A hydrolyses cAMP/cGMP signalling cascades, thus having a key role in the regulation of striatal output, and in promoting neuronal survival. PDE10A could be a key therapeutic target in Huntington's disease. Here, we used combined positron emission tomography (PET) and multimodal magnetic resonance imaging to assess PDE10A expression in vivo in a unique cohort of 12 early premanifest Huntington's disease gene carriers with a mean estimated 90% probability of 25 years before the predicted onset of clinical symptoms. We show bidirectional changes in PDE10A expression in premanifest Huntington's disease gene carriers, which are associated with the probability of symptomatic onset. PDE10A expression in early premanifest Huntington's disease was decreased in striatum and pallidum and increased in motor thalamic nuclei, compared to a group of matched healthy controls. Connectivity-based analysis revealed prominent PDE10A decreases confined in the sensorimotor-striatum and in striatonigral and striatopallidal projecting segments. The ratio between higher PDE10A expression in motor thalamic nuclei and lower PDE10A expression in striatopallidal projecting striatum was the strongest correlate with higher probability of symptomatic conversion in early premanifest Huntington's disease gene carriers. Our findings demonstrate in vivo, a novel and earliest pathophysiological mechanism underlying Huntington's disease with direct implications for the development of new pharmacological treatments, which can promote neuronal survival and improve outcome in Huntington's disease gene carriers.
Roussakis A-A, Politis M, Towey D, et al., 2015, Levodopa induced dyskinesias: increased serotonin to dopamine transporter ratios in the putamen of Parkinson's disease patients, 1st Congress of the European-Academy-of-Neurology, Publisher: Wiley, Pages: 195-195, ISSN: 1468-1331
Bastida AM, Politis M, Loane C, et al., 2015, Nigral iron susceptibility in Parkinson's disease (PD), 1st Congress of the European-Academy-of-Neurology, Publisher: WILEY, Pages: 67-67, ISSN: 1351-5101
Colasanti A, Guo Q, Giannetti P, et al., 2015, Hippocampal Inflammation and Depressive Symptoms are Associated to the Strength of Hippocampal Functional Connectivity in Multiple Sclerosis: A Study with TSPO-PET and Resting-State fMRI, 70th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology, Publisher: ELSEVIER SCIENCE INC, Pages: 115S-116S, ISSN: 0006-3223
Niccolini F, Foltynie T, Marques TR, et al., 2015, Loss of phosphodiesterase 10A signalling is associated with progression and severity in patients with Parkinson's disease, JOURNAL OF NUCLEAR MEDICINE, Vol: 56, ISSN: 0161-5505
Wu K, Politis M, O'Sullivan SS, et al., 2015, Single versus multiple impulse control disorders in Parkinson's disease: an C-11-raclopride positron emission tomography study of reward cue-evoked striatal dopamine release, Journal of Neurology, Vol: 262, Pages: 1504-1514, ISSN: 1432-1459
Impulse control disorders (ICDs) are reportedin Parkinson’s disease (PD) in association with dopaminergictreatment. Approximately 25 % of patients with ICDshave multiple co-occurring ICDs (i.e. more than one diagnosedICD). The extent to which dopaminergic neurotransmissionin PD patients with multiple ICDs differsfrom those with only one diagnosed ICD is unknown. Theaims of this study are: (1) to investigate dopamine neurotransmissionin PD patients diagnosed with multiple ICDs,single ICDs and non-ICD controls in response to rewardrelatedvisual cues using positron emission tomographywith 11C-raclopride. (2) to compare clinical features of theabove three groups. PD individuals with mulitple ICDs(n = 10), single ICD (n = 7) and no ICDs (n = 9) wererecruited and underwent two positron emission tomography(PET) scans with 11C-raclopride: one where they viewedneutral visual cues and the other where they viewed a rangeof visual cues related to different rewards. Individuals withboth multiple ICDs and single ICDs showed significantlygreater ventral striatal dopamine release compared to nonICDPD individuals in response to reward cues, but the twoICD groups did not differ from each other in the extent ofdopamine release. Subjects with multiple ICDs were,however, significantly more depressed, and had higherlevels of impulsive sensation-seeking compared to subjectswith single ICDs and without ICDs. This is the first studyto compare dopamine neurotransmission using PET neuroimagingin PD subjects with multiple vs. single ICDs.Our results suggest that striatal dopamine neurotransmissionis not directly related to the co-occurrence of ICDs inPD, potentially implicating non-dopaminergic mechanismslinked to depression; and suggest that physicians should bevigilant in managing depression in PD patients with ICDs
Smith R, Wu K, Hart T, et al., 2015, The role of pallidal serotonergic function in Parkinson's disease dyskinesias: a positron emission tomography study, NEUROBIOLOGY OF AGING, Vol: 36, Pages: 1736-1742, ISSN: 0197-4580
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- Citations: 35
Piccini P, Martin-Bastida A, 2015, Other Hypokinetic Parkinsonian Syndromes, Brain Mapping: An Encyclopedic Reference, Pages: 731-736, ISBN: 9780123973160
Roussakis AA, Politis M, Towey D, et al., 2015, Parkinson’s disease progression is associated with increased putaminal serotonin to dopamine transporter ratio: relevance for dyskinesias, American Academy of Neurology 67th Annual Meeting
Niccolini F, Marques TR, Haider S, et al., 2014, Brain phosphodiesterase 10A (PDE-10A) density in early premanifest HD gene carriers, 28th Annual Meeting of the Blue-Ribbon-Section of the Movement-Disorders-Society, Publisher: WILEY-BLACKWELL, Pages: 1842-1842, ISSN: 0885-3185
Giannetti P, Politis M, Su P, et al., 2014, Increased PK11195-PET binding in normal-appearing white matter in clinically isolated syndrome, Brain, Vol: 138, Pages: 110-119, ISSN: 0006-8950
Wilkinson L, Tai YF, Lin CS, et al., 2014, Probabilistic Classification Learning With Corrective Feedback is Associated With in vivo Striatal Dopamine Release in the Ventral Striatum, While Learning Without Feedback is Not, HUMAN BRAIN MAPPING, Vol: 35, Pages: 5106-5115, ISSN: 1065-9471
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- Citations: 20
Colasanti A, Guo Q, Muhlert N, et al., 2014, In Vivo Assessment of Brain White Matter Inflammation in Multiple Sclerosis with <SUP>18</SUP>F-PBR111 PET, JOURNAL OF NUCLEAR MEDICINE, Vol: 55, Pages: 1112-1118, ISSN: 0161-5505
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- Citations: 78
Colasanti A, Guo Q, Giannetti P, et al., 2014, TSPO-targeted PET Imaging Suggests Increased Microglia Activation in Multiple Sclerosis Hippocampus is Correlated to Depressive Symptomatology, 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry, Publisher: ELSEVIER SCIENCE INC, Pages: 94S-95S, ISSN: 0006-3223
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- Citations: 1
Giannetti P, Politis M, Su P, et al., 2014, Microglia activation in multiple sclerosis black holes predicts outcome in progressive patients: An in vivo [(11)C](R)-PK11195-PET pilot study, NEUROBIOLOGY OF DISEASE, Vol: 65, Pages: 203-210, ISSN: 0969-9961
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- Citations: 61
Dexter DT, Martin-Bastida A, Kabba C, et al., 2014, A pilot 6 months efficacy and safety study utilising the iron chelator deferiprone in early stage Parkinson's disease, 18th International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY-BLACKWELL, Pages: S234-S234, ISSN: 0885-3185
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- Citations: 2
Niccolini F, Marques TR, Haider S, et al., 2014, Brain phosphodiesterase 10A (PDE-10A) density in early premanifest HD gene carriers, 18th International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY-BLACKWELL, Pages: S212-S213, ISSN: 0885-3185
Wu K, Politis M, O'Sullivan SS, et al., 2014, Problematic Internet use in Parkinson's disease, PARKINSONISM & RELATED DISORDERS, Vol: 20, Pages: 482-487, ISSN: 1353-8020
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- Citations: 14
Politis M, Wu K, Loane C, et al., 2014, Serotonergic mechanisms responsible for levodopa-induced dyskinesias in Parkinson's disease patients, Journal of Clinical Investigation, Vol: 124, Pages: 1340-1349, ISSN: 0021-9738
Levodopa-induced dyskinesias (LIDs) are the most common and disabling adverse motor effect of therapy in Parkinson’s disease (PD) patients. In this study, we investigated serotonergic mechanisms in LIDs development in PD patients using 11C-DASB PET to evaluate serotonin terminal function and 11C-raclopride PET to evaluate dopamine release. PD patients with LIDs showed relative preservation of serotonergic terminals throughout their disease. Identical levodopa doses induced markedly higher striatal synaptic dopamine concentrations in PD patients with LIDs compared with PD patients with stable responses to levodopa. Oral administration of the serotonin receptor type 1A agonist buspirone prior to levodopa reduced levodopa-evoked striatal synaptic dopamine increases and attenuated LIDs. PD patients with LIDs that exhibited greater decreases in synaptic dopamine after buspirone pretreatment had higher levels of serotonergic terminal functional integrity. Buspirone-associated modulation of dopamine levels was greater in PD patients with mild LIDs compared with those with more severe LIDs. These findings indicate that striatal serotonergic terminals contribute to LIDs pathophysiology via aberrant processing of exogenous levodopa and release of dopamine as false neurotransmitter in the denervated striatum of PD patients with LIDs. Our results also support the development of selective serotonin receptor type 1A agonists for use as antidyskinetic agents in PD.
Politis M, Wu K, Loane C, et al., 2014, Serotonergic mechanisms responsible for levodopa-induced dyskinesias in Parkinson's disease patients., The Journal of clinical investigation, Vol: 124, Pages: 1340-1349
Levodopa-induced dyskinesias (LIDs) are the most common and disabling adverse motor effect of therapy in Parkinson's disease (PD) patients. In this study, we investigated serotonergic mechanisms in LIDs development in PD patients using 11C-DASB PET to evaluate serotonin terminal function and 11C-raclopride PET to evaluate dopamine release. PD patients with LIDs showed relative preservation of serotonergic terminals throughout their disease. Identical levodopa doses induced markedly higher striatal synaptic dopamine concentrations in PD patients with LIDs compared with PD patients with stable responses to levodopa. Oral administration of the serotonin receptor type 1A agonist buspirone prior to levodopa reduced levodopa-evoked striatal synaptic dopamine increases and attenuated LIDs. PD patients with LIDs that exhibited greater decreases in synaptic dopamine after buspirone pretreatment had higher levels of serotonergic terminal functional integrity. Buspirone-associated modulation of dopamine levels was greater in PD patients with mild LIDs compared with those with more severe LIDs. These findings indicate that striatal serotonergic terminals contribute to LIDs pathophysiology via aberrant processing of exogenous levodopa and release of dopamine as false neurotransmitter in the denervated striatum of PD patients with LIDs. Our results also support the development of selective serotonin receptor type 1A agonists for use as antidyskinetic agents in PD.
Colasanti A, Piccini P, 2014, PET imaging in multiple sclerosis: Focus on the translocator protein, Pet and Spect in Neurology, Pages: 757-773, ISBN: 9783642543067
PET imaging offers the potential of high specifi city for molecular markers of neuroinfl ammatory processes in Multiple Sclerosis. The most extensively characterized target is the 18 KDa translocator protein (TSPO). Autoradiography studies suggested that TSPO density mainly refl ects activated microglia in Multiple Sclerosis patients’ brain. PET studies showed an increased TSPO signal in the white and gray matter of MS patients, that correlated with disease severity. New generation TSPO PET tracers with improved imaging characteristics are promising, but require further characterization to clarify their full potential for application in Multiple Sclerosis. With the development and validation of a wider range of molecular targets, the impact of PET imaging on the progress of neurobiological research in Multiple Sclerosis could become potentially crucial.
Kefalopoulou Z, Politis M, Piccini P, et al., 2014, Long-term Clinical Outcome of Fetal Cell Transplantation for Parkinson Disease Two Case Reports, JAMA NEUROLOGY, Vol: 71, Pages: 83-87, ISSN: 2168-6149
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- Citations: 197
Colasanti A, Guo Q, Mulhert N, et al., 2013, [18F]PBR111 binding in lesional and peri-lesional multiple sclerosis white matter, 29th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis / 18th Annual Conference of Rehabilitation in MS, Publisher: SAGE PUBLICATIONS LTD, Pages: 68-69, ISSN: 1352-4585
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