Publications
280 results found
Roussakis A-A, Towey D, Piccini P, 2017, Changes over time in striatal DAT availability in Parkinson's disease: Relevance to levodopa-induced dyskinesias, 3rd Congress of the European-Academy-of-Neurology, Publisher: WILEY, Pages: 661-661, ISSN: 1351-5101
Bastida AM, Lao-Kaim NP, Xing Y, et al., 2017, Assessing longitudinal iron deposition in deep grey matter nuclei with high-pass filtered phase MR Imaging in Parkinson's disease, 3rd Congress of the European-Academy-of-Neurology, Publisher: WILEY, Pages: 427-427, ISSN: 1351-5101
Bastida AM, Xing Y, Pietracupa S, et al., 2017, Resting state nigral functional connectivity in Parkinson's disease: A cross-sectional study, 3rd Congress of the European-Academy-of-Neurology, Publisher: WILEY, Pages: 428-428, ISSN: 1351-5101
Li W, Lao-Kaim N, Roussakis A, et al., 2017, 11C-PE2I and 18F-DOPA PET imaging for assessing the severity and rate of progression in Parkinson's disease: The longitudinal study, 3rd Congress of the European-Academy-of-Neurology, Publisher: WILEY, Pages: 593-593, ISSN: 1351-5101
Martin-Bastida A, Xing Y, Pietracupa S, et al., 2017, Assessing Nigral Functional Connectivity in Parkinson's disease With Resting State Functional MRI, 21st International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY, ISSN: 0885-3185
Roussakis AA, Towey D, Piccini P, 2017, SPECT imaging of striatal DAT availability in Parkinson's disease: Changes over time and relevance to dyskinesias, 21st International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY, ISSN: 0885-3185
Roussakis AA, Lao-Kaim N, Martin-Bastida A, et al., 2017, Serotonin-to-dopamine transporter ratios in Parkinson's dyskinesias: The longitudinal study, 21st International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY, ISSN: 0885-3185
Li W, Lao-Kaim N, Roussakis A-A, et al., 2017, Longitudinal comparison of 11C-PE2I and 18F-DOPA PET for assessing severity and rate of disease progression in patients with Parkinson's disease, 21st International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY, ISSN: 0885-3185
Martin-Bastida A, Lao-Kaim N, Xing Y, et al., 2017, High-Pass Filtered Phase Mr Imaging to Detect Longitudinal Motor Associations of Iron Accumulation in Parkinson's Disease, 21st International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY, ISSN: 0885-3185
Martin-Bastida A, Pietracupa S, Piccini P, 2017, Neuromelanin in parkinsonian disorders: an update., International Journal of Neuroscience, Vol: 127, Pages: 1116-1123, ISSN: 0020-7454
Neuromelanin (NM) is a dark pigment that accumulates linearly with aging in substantia nigra (SN) and locus coeruleus (LC). The dual protective and toxic role of NM has been hypothesized according to its intraneuronal or extraneuronal deposition. The melanized dopaminergic neurons in SN and LC seem to have special vulnerability to neurodegeneration in Parkinson's disease (PD). The paramagnetic properties of NM due to its association to metals like iron induce T1 prolongation; hence the measurement of SN-sensitive contrast could be a useful diagnostic biomarker in neurodegenerative disease like PD and other atypical parkinsonisms. This paper will review NM histopathology and neurochemistry studies in health and diseases and the role of imaging targeting NM load in parkinsonian disorders.
Martin-Bastida A, Ward RJ, Newbould R, et al., 2017, Brain iron chelation by deferiprone in a phase 2 randomised double-blinded placebo controlled clinical trial in Parkinson's disease, Scientific Reports, Vol: 7, ISSN: 2045-2322
Parkinson’s disease (PD) is associated with increased iron levels in the substantia nigra (SNc). This study evaluated whether the iron chelator, deferiprone, is well tolerated, able to chelate iron from various brain regions and improve PD symptomology. In a randomised double-blind, placebo controlled trial, 22 early onset PD patients, were administered deferiprone, 10 or 15 mg/kg BID or placebo, for 6 months. Patients were evaluated for PD severity, cognitive function, depression rating and quality of life. Iron concentrations were assessed in the substantia nigra (SNc), dentate and caudate nucleus, red nucleus, putamen and globus pallidus by T2* MRI at baseline and after 3 and 6 months of treatment. Deferiprone therapy was well tolerated and was associated with a reduced dentate and caudate nucleus iron content compared to placebo. Reductions in iron content of the SNc occurred in only 3 patients, with no changes being detected in the putamen or globus pallidus. Although 30 mg/kg deferiprone treated patients showed a trend for improvement in motor-UPDRS scores and quality of life, this did not reach significance. Cognitive function and mood were not adversely affected by deferiprone therapy. Such data supports more extensive clinical trials into the potential benefits of iron chelation in PD.
Strafella AP, Bohnen NI, Perlmutter JS, et al., 2017, Molecular imaging to track Parkinson's disease and atypical parkinsonisms: New imaging frontiers, MOVEMENT DISORDERS, Vol: 32, Pages: 181-192, ISSN: 0885-3185
Martin-Bastida A, Lao-Kaim NP, Loane C, et al., 2016, Motor associations of iron accumulation in deep grey matter nuclei in Parkinson's disease: a cross-sectional study of iron-related magnetic resonance imaging susceptibility., European Journal of Neurology, Vol: 24, Pages: 357-365, ISSN: 1468-1331
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.
Politis M, Lahiri N, Niccolini F, et al., 2016, Increased central microglial activation associated with peripheral cytokine levels in premanifest Huntington's disease gene carriers (vol 83, pg 115, 2015), NEUROBIOLOGY OF DISEASE, Vol: 98, Pages: 162-162, ISSN: 0969-9961
Roussakis A-A, Lao-Kaim N, Martin-Bastida A, et al., 2016, LEVODOPA-INDUCED DYSKINESIA IN PARKINSON'S: A LONGITUDINAL PET STUDY, Annual Meeting of the Association-of-British-Neurologists (ABN), Publisher: BMJ PUBLISHING GROUP, ISSN: 0022-3050
Rolinski M, Griffanti L, Piccini P, et al., 2016, Basal ganglia dysfunction in idiopathic REM sleep behaviour disorder parallels that in early Parkinson’s disease, Brain, Vol: 139, Pages: 2224-2234, ISSN: 0006-8950
Resting-state fMRI (rs-fMRI) dysfunction within the basal ganglia network (BGN) is a feature of early Parkinson’s disease (Szewczyk-Krolikowski et al., 2014, Rolinski et al., 2015), and may be a diagnostic biomarker of basal ganglia dysfunction. Currently, it is unclear whether these changes are present in so-called idiopathic rapid eye movement sleep behaviour disorder (RBD), a condition associated with a high rate of future conversion to Parkinson’s. In this study, we explore the utility of rs-fMRI to detect BGN dysfunction in RBD. We compare these data to a set of healthy controls, and to a set of patients with established early Parkinson’s. Furthermore, we explore the relationship between rs-fMRI BGN dysfunction and loss of dopaminergic neurons assessed with dopamine transporter single photon emission computerised tomography (SPECT), and perform morphometric analyses to assess grey matter loss.26 patients with polysomnographically established RBD, 48 Parkinson’s patients and 23 healthy controls were included in this study. Resting-state networks were isolated from task-free fMRI data using dual regression with a template was derived from a separate cohort of 80 elderly HC participants. Rs-fMRI parameter estimates were extracted from the study subjects in the BGN. In addition, 8 RBD, 10 Parkinson’s and 10 control subjects received 123I-ioflupane SPECT. We tested for reduction of BGN connectivity, and for loss of tracer uptake in RBD and Parkinson’s relative to each other and to controls. Connectivity measures of BGN network dysfunction differentiated both RBD and Parkinson’s from controls with high sensitivity (96%) and specificity (74% for RBD, 78% for PD), indicating its potential as an indicator of early basal ganglia dysfunction. RBD was indistinguishable from Parkinson’s on rs-fMRI despite obvious differences on dopamine transported SPECT. Basal ganglia connectivity is a promising biomarker for the detection of
Colasanti A, Guo Q, Giannetti P, et al., 2016, Neuroinflammation and genesis of affective symptoms in multiple sclerosis: integrating evidence from TSPO PET and resting state FMRI, Bipolar Disorders, Vol: 18, Pages: 84-84, ISSN: 1398-5647
Roussakis AA, Lao-Kaim, Martin-Bastida A, et al., 2016, Increased serotonin-to-dopamine transporter ratios in Parkinson disease dyskinesias: a longitudinal study, 2nd Congress of the European Academy of Neurology, Publisher: Wiley, Pages: 105-105, ISSN: 1468-1331
Background and aimsSerotonergic terminals play an important role in levodopa-induced dyskinesias (LIDs) in patients with Parkinson’s disease (PD). An increased SERT-over-DAT terminal ratio in the putamen has been proposed to be a risk factor for the appearance of LIDs. We investigated the temporal relationship between serotonergic terminal changes and dopaminergic loss in the putamen and the appearance of LIDs.MethodsTwelve PD patients underwent PET with 11C-DASB and 11C-PE2I; which are specific in vivo markers of serotonin (SERT) and dopamine transporters (DAT),respectively. All patients repeated 11C-DASB and 11C-PE2I PET after 17 months(±11 weeks).The simplified reference tissue model was employed using the cerebellum as a reference. 11C-DASB binding potential (BP), 11C-PE2I BP and 11C-DASB-to-11C-PE2I BP ratios were calculated.ResultsAt baseline, all PD patients were non-dyskinetic. The mean 11C-DASB BP was 1.28(±0.14), the mean 11C-PE2I BP was 1.63(±0.41), and the median of the SERT-to-DAT ratio was 0.779(±0.19).At follow-up, the mean 11C-PE2I BP was (1.39±0.41) reduced by 14.52% from baseline (p<0.001); the 11C-DASB BP had only reduced by 4.32% (1.23±0.19)(p>0.10). Percentage changes in 11C-PE2I BP at follow-up were significantly greater than percentage changes in 11C-DASB BP (p<0.05). The SERT-to-DAT ratios significantly increased by 12.76% (p<0.01) over this time. Three PD patients became dyskinetic;their SERT-to-DAT ratios were 0.978, 0.878, and 1.282.ConclusionThe imbalance in the rate of SERT and DAT decline reflects the increase of the SERT–to–DAT ratio over time. Our findings suggest that there may be a threshold of SERT-over-DAT availability in the putamen, above which PD patients are likely to become dyskinetic.
Martin-Bastida A, Lao-Kaim NP, Roussakis AA, et al., 2016, Multimodal imaging assessment of nigrostriatal pathway in Parkinson's disease using 11C-PE2I PET and neuromelanin-sensitive MR, 20th International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY-BLACKWELL, Pages: S408-S409, ISSN: 0885-3185
Pietracupa S, Martin-Bastida A, Kaim NL, et al., 2016, Neuromelanin in Parkinson's disease: A 3T MRI study, 20th International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY-BLACKWELL, Pages: S402-S402, ISSN: 0885-3185
Li W, Lao-Kaim NP, Roussakis AA, et al., 2016, Comparison of DAT and DOPA PET tracer for assessing severity and progression in patients with Parkinson's disease, 20th International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY-BLACKWELL, Pages: S409-S409, ISSN: 0885-3185
Niccolini F, Foltynie T, Marques TR, et al., 2016, LOSS OF PHOSPHODIESTERASE 10A SIGNALLING IS ASSOCIATED WITH PROGRESSION AND SEVERITY IN PATIENTS WITH PARKINSON'S DISEASE, 27th International Symposium on Cerebral Blood Flow, Metabolism and Function / 12th International Conference on Quantification of Brain Function with PET, Publisher: SAGE PUBLICATIONS INC, Pages: 107-108, ISSN: 0271-678X
Bastida AM, Lao-Kaim N, Roussakis A-A, et al., 2016, Imaging nigrostriatal circuitry with 11C-PE2I PET and neuromelanin-sensitive MR in Parkinson's disease, Publisher: WILEY, Pages: 920-920, ISSN: 1351-5101
Loane C, Politis M, Kefalopoulou Z, et al., 2016, Aberrant nigral diffusion in Parkinson's disease: A longitudinal diffusion tensor imaging study, Movement Disorders, Vol: 31, Pages: 1020-1026, ISSN: 1531-8257
BackgroundMeasuring microstructure alterations with diffusion tensor imaging in PD is potentially a valuable tool to use as a biomarker for early diagnosis and to track disease progression. Previous studies have reported a specific decrease of nigral fractional anisotropy in PD. However, to date the effect of disease progression on nigral or striatal diffusion indices has not been fully explored.MethodsWe have conducted a cross-sectional and longitudinal diffusion tensor imaging study in 18 early stage, treated PD patients and 14 age-matched controls. PD patients were scanned on 2 occasions OFF medication, 19.3 months apart (standard deviation = 3.1 months). Longitudinal change of regional nigral and striatal measures of fractional anisotropy and mean diffusivity were calculated using a region-of-interest approach.ResultsRegion-of-interest analysis demonstrated that at baseline, PD patients and controls did not differ in regard to diffusion indices in any region assessed. A significant difference of nigral fractional anisotropy and mean diffusivity between controls and PD patients at follow-up was detected and confirmed with longitudinal analysis within PD patients. Alterations in striatal regions were not detected in either group or over time.ConclusionOur findings indicate that nigral diffusion measure may be a valuable measure of disease progression. In the future, larger longitudinal studies will confirm whether diffusion indices may serve as sensitive and clinically meaningful measures of disease progression in PD.
Bastida A, Ward R, Piccini P, et al., 2016, SYSTEMIC INFLAMMATION INFLUENCES THE ABILITY OF DEFERIPRONE TO CHELATE IRON FROM SPECIFIC BRAIN REGIONS IN PARKINSON'S DISEASE PATIENTS, AMERICAN JOURNAL OF HEMATOLOGY, Vol: 91, Pages: E232-E232, ISSN: 0361-8609
Roussakis AA, Politis M, Towey D, et al., 2016, Serotonin-to-dopamine transporter ratios in Parkinson disease: Relevance for dyskinesias., Neurology, Vol: 86, Pages: 1152-1158, ISSN: 1526-632X
OBJECTIVE: To investigate whether a serotonin-to-dopamine terminal ratio is related to the appearance of dyskinesias in patients with Parkinson disease (PD). METHODS: Twenty-eight patients with idiopathic PD (17 with levodopa-induced dyskinesias [LIDs], 11 without dyskinesias) and 12 age-matched healthy controls were studied with PET and 5[(11)C]-3-amino-4-(2-dimethylaminomethylphenyl-sulfanyl)-benzonitrile ((11)C-DASB) and with SPECT and [(123)I]N-w-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ((123)I-ioflupane), which are in vivo specific markers of the serotonin and dopamine transporters' availability, respectively. We have employed a simplified reference tissue model for the quantification of (11)C-DASB, whereas a semiquantification approach was used for (123)I-ioflupane data. We calculated (11)C-DASB binding to (123)I-ioflupane uptake ratios for the caudate and the putamen. RESULTS: Patients with PD showed striatal decreases in (11)C-DASB binding potential (p < 0.01) and in (123)I-ioflupane mean uptake (p < 0.001) compared to controls. The mean (11)C-DASB binding to (123)I-ioflupane uptake ratio in the putamen was 0.779 (increased by 75.8% of the controls' mean) for the nondyskinetic group and 0.901 (increased by 103.4% of the controls' mean) for the patients with dyskinesias. There was a statistically significant difference (p < 0.001) in (11)C-DASB binding to (123)I-ioflupane uptake ratio in the putamen between the group of patients with and without dyskinesias. Higher (11)C-DASB to (123)I-ioflupane binding ratios correlated with longer disease duration for the 28 patients with PD (r = 0.52; p < 0.01). CONCLUSIONS: Serotonin-to-dopamine transporter binding ratio increases as PD progresses and patients experience LIDs. Our findings suggest that, when the dopaminergic innervation in the striatum is critically low, the serotonergic system plays an important role in development of LIDs.
Roussakis A-A, Piccini P, 2015, PET imaging in Huntington’s disease, Journal of Huntington's Disease, Vol: 4, Pages: 287-296, ISSN: 1879-6400
Colasanti A, Guo, Giannetti P, et al., 2015, Hippocampal neuroinflammation, functional connectivity and depressive symptoms in multiple sclerosis, Biological Psychiatry, Vol: 80, Pages: 62-72, ISSN: 1873-2402
BackgroundDepression, a condition commonly comorbid with multiple sclerosis (MS), is associated more generally with elevated inflammatory markers and hippocampal pathology. We hypothesized that neuroinflammation in the hippocampus is responsible for depression associated with MS. We characterized the relationship between depressive symptoms and hippocampal microglial activation in patients with MS using the 18-kDa translocator protein radioligand [18F]PBR111. To evaluate pathophysiologic mechanisms, we explored the relationships between hippocampal neuroinflammation, depressive symptoms, and hippocampal functional connectivities defined by resting-state functional magnetic resonance imaging.MethodsThe Beck Depression Inventory (BDI) was administered to 11 patients with MS and 22 healthy control subjects before scanning with positron emission tomography and functional magnetic resonance imaging. We tested for higher [18F]PBR111 uptake in the hippocampus of patients with MS relative to healthy control subjects and examined the correlations between [18F]PBR111 uptake, BDI scores, and hippocampal functional connectivities in the patients with MS.ResultsPatients with MS had an increased hippocampal [18F]PBR111 distribution volume ratio relative to healthy control subjects (p = .024), and the hippocampal distribution volume ratio was strongly correlated with the BDI score in patients with MS (r = .86, p = .006). Hippocampal functional connectivities to the subgenual cingulate and prefrontal and parietal regions correlated with BDI scores and [18F]PBR111 distribution volume ratio.ConclusionsOur results provide evidence that hippocampal microglial activation in MS impairs the brain functional connectivities in regions contributing to maintenance of a normal affective state. Our results suggest a rationale for the responsiveness of depression in some patients with MS to effective control of brain neuroinflammation. Our findings also lend support to further investigation of t
Pellicano C, Niccolini F, Wu K, et al., 2015, Morphometric changes in the reward system of Parkinson's disease patients with impulse control disorders, JOURNAL OF NEUROLOGY, Vol: 262, Pages: 2653-2661, ISSN: 0340-5354
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Ruffmann C, Calboli FC, Bravi I, et al., 2015, Cortical Lewy bodies and Aβ burden are associated with prevalence and timing of dementia in Lewy body diseases., Neuropathology and Applied Neurobiology, Vol: 42, Pages: 436-450, ISSN: 1365-2990
AIMS: Our main objective was to determine the neuropathological correlates of dementia in patients with Lewy body disease (LBD). Furthermore, we used data derived from clinical, neuropathological and genetic studies to investigate boundary issues between Dementia with Lewy bodies (DLB) and Parkinson's disease with (PDD) and without (PDND) dementia. METHODS: 121 cases with a neuropathological diagnosis of LBD and clinical information on dementia status were included in the analysis (55 PDD, 17 DLB and 49 PDND). We carried out topographical and semi-quantitative assessment of Lewy bodies (LB), Aβ plaques and tau-positive neuropil threads (NT). The APOE genotype and MAPT haplotype status were also determined. RESULTS: The cortical LB (CLB) burden was the only independent predictor of dementia (OR: 4.12, p<0.001). The total cortical Aβ plaque burden was an independent predictor of a shorter latency to dementia from onset of motor signs (p=0.001). DLB cases had a higher LB burden in the parietal and temporal cortex, compared to PDD. Carrying at least one APOE ϵ4 allele was associated with a higher cortical LB burden (p=0.02), particularly in the neocortical frontal, parietal, and temporal regions. CONCLUSIONS: High CLB burden is a key neuropathological substrate of dementia in LBD. Elevated cortical LB pathology and Aβ plaque deposition are both correlated with a faster progression to dementia. The higher CLB load in the temporal and parietal regions, which seems to be a distinguishing feature of DLB, may account for the shorter latency to dementia and could be mediated by the APOE ϵ4 allele. This article is protected by copyright. All rights reserved.
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