Publications
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Lao-Kaim NP, Martin-Bastida A, Roussakis A-A, et al., 2019, Multimodal imaging of neuromelanin and dopamine transporters in Parkinson's disease reveals asymmetrical relationships within the nigrostriatal system, 5th Congress of the European-Academy-of-Neurology (EAN), Publisher: WILEY, Pages: 99-99, ISSN: 1351-5101
Hannaway N, Lao-Kaim NP, Martin-Bastida A, et al., 2019, Functional responses to joystick movements during Parkinson's disease progression: a longitudinal fMRI study, 5th Congress of the European-Academy-of-Neurology (EAN), Publisher: WILEY, Pages: 227-227, ISSN: 1351-5101
Roussakis A-A, Mohamed MA, Myers J, et al., 2019, Astrogliosis in Parkinson's disease dementia: a preliminary report with brain, 5th Congress of the European-Academy-of-Neurology (EAN)
Roussakis A, Gennaro M, Lao-Kaim N, et al., 2019, Dopamine transporter density in de novo Parkinson’s disease does not relate to the development of levodopa-induced dyskinesias, Journal of Neuroinflammation and Neurodegenerative Diseases, Vol: 3
Background: In Parkinson’s disease (PD), the onset of levodopa-induced dyskinesias (LIDs) is difficult to predict. This study examines whether dopamine transporter (DAT)-specific SPECT imaging in de novo PD relates to later development of LIDs.Methods: 42 de novo unilateral PD participants received DAT-specific SPECT imaging with 123I-FP-CIT at time of diagnosis. At five years post-diagnosis, all PD patients were clinically evaluated and divided into two groups based on whether they had or had not developed LIDs. Fourteen gender- and age-matched healthy volunteers undertook 123I-FP-CIT SPECT imaging and were included as controls. A semi-quantification approach was used for the 123I-FP-CIT data using the occipital cortex as the reference region. We calculated specific binding ratios (SBR) for the caudate and putamen (posterior and anterior putaminal subregions). In parallel, we analysed our 123I-FP-CIT dataset with a voxel-based analysis approach.Results: PD patients had significantly lower striatal 123I-FP-CIT SBR values in comparison to controls (p<0.001). After five years, dyskinetic patients (N=10) were taking higher daily doses of dopaminergic medication (p<0.001) and had more severe disease (difference in Hoehn & Yahr staging scores p<0.05) as compared to the nondyskinetic group (N=32). At the time of diagnosis, 123I-FP-CIT SBR values were not statistically different between the two groups for all striatal regions (p>0.05). SPM voxel-based analysis did not show a statistically significant difference between the two groups (p>0.05).Conclusion: 123I-FP-CIT SPECT imaging, performed at diagnosis in de novo early-stage PD could not differentiate patients who will develop LIDs within five years from those who will not.
Reilmann R, Gordon MF, Anderson KE, et al., 2019, The Efficacy and Safety Results of Laquinimod as a Treatment for Huntington Disease (LEGATO-HD), 71st Annual Meeting of the American-Academy-of-Neurology (AAN), Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0028-3878
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Maxan A, Mason S, Saint-Pierre M, et al., 2018, Outcome of cell suspension allografts in a patient with Huntington's disease, Annals of Neurology, Vol: 84, Pages: 950-956, ISSN: 0364-5134
For patients with incurable neurodegenerative disorders such as Huntington's (HD) and Parkinson's disease, cell transplantation has been explored as a potential treatment option. Here, we present the first clinicopathological study of a patient with HD in receipt of cell-suspension striatal allografts who took part in the NEST-UK multicenter clinical transplantation trial. Using various immunohistochemical techniques, we found a discrepancy in the survival of grafted projection neurons with respect to grafted interneurons as well as major ongoing inflammatory and immune responses to the grafted tissue with evidence of mutant huntingtin aggregates within the transplant area. Our results indicate that grafts can survive more than a decade post-transplantation, but show compromised survival with inflammation and mutant protein being observed within the transplant site. Ann Neurol 2018; 1-7.
Martin-Bastida A, Lao-Kaim N, Pietracupa S, et al., 2018, Assessing working memory dysfunction with letter n-back functional MRI task in early-stage Parkinson's disease, International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY, Pages: S688-S688, ISSN: 0885-3185
Martin-Bastida A, Lao-Kaim N, Pietracupa S, et al., 2018, Compensatory functional activations in early-stage Parkinson's disease: A cross-sectional motor planning fMRI study, International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY, Pages: S653-S653, ISSN: 0885-3185
Li W, Lao-Kaim N, Roussakis A, et al., 2018, Functional connectivity changes in relation to dopaminergic decline in Parkinson's over time: A resting-state fMRI and 11C-PE2I PET imaging study, International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY, Pages: S682-S683, ISSN: 0885-3185
Roussakis AA, Lao-Kaim N, Martin-Bastida A, et al., 2018, A longitudinal PET study to assess progression of laterality in Parkinson's disease, International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY, Pages: S690-S690, ISSN: 0885-3185
Gordon MF, Reilmann R, Anderson K, et al., 2018, Legato-HD Study: A Phase 2 Study Assessing the Efficacy and Safety of Laquinimod as a Treatment for Huntington Disease, 47th Annual Meeting of the Child-Neurology-Society (CNS), Publisher: WILEY, Pages: S190-S190, ISSN: 0364-5134
Reilmann R, Gordon MF, Anderson KE, et al., 2018, Legato-HD Study: a Phase 2 Study Assessing the Efficacy and Safety of Laquinimod as a Treatment for Huntington Disease, Publisher: SPRINGER, Pages: 1192-1193, ISSN: 1933-7213
Xing Y, Schwarz S, Martin-Bastida A, et al., 2018, Semi-automated segmentation and quantification of the substantia nigra depigmentation in Parkinson's disease - a multicentre case control MRI study in 284 participants, International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY, Pages: S691-S692, ISSN: 0885-3185
Roussakis A, Piccini P, 2018, Molecular imaging of neuroinflammation in idiopathic Parkinson's Disease, International Review of Neurobiology, Vol: 141, Pages: 347-363, ISSN: 0074-7742
Neuroinflammation is an important aspect of Parkinson's disease. The study of Parkinson's disease neuroinflammation is quite challenging and is accompanied by controversy. To date, molecular imaging studies have been targeting microglia and more recently astrocytes. In this review article, we discuss the findings from key PET studies with tracers specific for the translocator protein (microglia-specific) and novel evidence from the development of astrocyte-specific PET tracers. We also discuss evidence from pathology studies and in the animal model of Parkinson's disease that form the biological background of current and newer PET neuroinflammation tracers. However, findings from PET imaging studies in microglia have so far not been translated in clinical practice, while no PET study has been conducted in Parkinson's disease specifically targeting astrocytes. Research work is currently focused on (a) identifying new molecular targets for the study of neuroinflammation through PET, (b) assessing the state of neuroinflammation in Parkinson's disease with accuracy and reliability, and (c) developing strategies to modulate the underlying processes of neuroinflammation.
Reilmann R, Gordon MF, Anderson KE, et al., 2018, LEGATO-HD STUDY: A PHASE 2 STUDY ASSESSING THE EFFICACY AND SAFETY OF LAQUINIMOD AS A TREATMENT FOR HUNTINGTON DISEASE, Plenary Meeting of the European-Huntington's-Disease-Network (EHDN), Publisher: BMJ PUBLISHING GROUP, Pages: A99-A99, ISSN: 0022-3050
Lee J-Y, Lao-Kaim NP, Pasquini J, et al., 2018, Pallidal dopaminergic denervation and rest tremor in early Parkinson's disease: PPMI cohort analysis, Parkinsonism and Related Disorders, Vol: 51, Pages: 101-104, ISSN: 1353-8020
BACKGROUND: s: Over recent years there have been some conflicting reports upon the role of pallidal dopaminergic denervation in rest tremor in Parkinson's disease. OBJECTIVES: To clarify this issue we analyzed the clinical and 123I-FP-CIT SPECT data of a large cohort of early Parkinson's disease patients enrolled in the PPMI study. METHODS: Pallidal and striatal dopamine transporter uptake ratios were calculated in 382 patients (120 no-tremor, 60 tremor-dominant, and 202 indeterminate) and 150 controls. A region of interest (ROI) approach was used to estimate DAT uptake ratios from 123I-FP-CIT SPECT scans in the caudate nucleus, putamen, and globus pallidus after normalization to a DAT template. DAT uptake ratios for each region were compared between subgroups using ANCOVA and linear regression analyses were performed to evaluate the relationship between severity of rest tremor and regional DAT uptake ratios. RESULTS: PD patients had significantly lower DAT uptake ratios in the pallidum, putamen and caudate as compared to healthy controls (p < 0.001). ANCOVA showed inter-PD subgroup differences in DAT uptake ratios in the putamen and pallidum (p < 0.05) after adjustment for age and disease duration, with post-hoc comparisons revealing significantly higher DAT uptake ratios for the tremor-dominant subgroup as compared to non-tremor and indeterminate subgroups (p < 0.016). There was no significant relationship between rest tremor severity and pallidal DAT either in the tremor-dominant subgroup or in the total PD population. CONCLUSIONS: Pallidal dopaminergic denervation appears unrelated to rest tremor severity in early Parkinson's disease.
Li W, Lao-Kaim NP, Roussakis A, et al., 2018, Functional connectivity changes in relation to dopaminergic decline in Parkinson's over time: a resting-state fMRI and 11C-PE2I PET imaging study, 4th Congress of the European-Academy-of-Neurology (EAN), Publisher: WILEY, Pages: 345-345, ISSN: 1351-5101
Reilmann R, Gordon MF, Anderson K, et al., 2018, Update on the LEGATO-HD Study: A Phase II Study Assessing the Efficacy and Safety of Laquinimod as a Treatment for Huntington's Disease, Publisher: SPRINGER, Pages: 260-261, ISSN: 1933-7213
Schwarz ST, Xing Y, Naidu S, et al., 2017, Protocol of a single group prospective observational study on the diagnostic value of 3T susceptibility weighted MRI of nigrosome-1 in patients with parkinsonian symptoms: the N3iPD study (nigrosomal iron imaging in Parkinson's disease), BMJ Open, Vol: 7, ISSN: 2044-6055
Introduction: Parkinson’s disease (PD) is the most common movement disorder in the elderly and is characterised clinically by bradykinesia, tremor and rigidity. Diagnosing Parkinson’s can be difficult especially in the early stages. High-resolution nigrosome MRI offers promising diagnostic accuracy of patients with established clinical symptoms; however, it is unclear whether this may help to establish the diagnosis in the early stages of PD, when there is diagnostic uncertainty. In this scenario, a single photon emission CT scan using a radioactive dopamine transporter ligand can help to establish the diagnosis, or clinical follow-up may eventually clarify the diagnosis. A non-invasive, cost-effective diagnostic test that could replace this would be desirable. We therefore aim to prospectively test whether nigrosome MRI is as useful as DaTSCAN to establish the correct diagnosis in people with minor or unclear symptoms suspicious for PD.Methods and analysis: In a prospective study we will recruit 145 patients with unclear symptoms possibly caused by Parkinson’s from three movement disorder centres in the UK to take part in the study. We will record the Movement Disorder Society - Unified Parkinson’s Disease Rating Scale, and participants will undergo DaTSCAN and high-resolution susceptibility weighted MRI at a field strength of 3T. DaTSCANs will be assessed visually and semiquantitatively; MRI scans will be visually assessed for signal loss in nigrosome-1 by blinded investigators. We will compare how the diagnosis suggested by MRI compares with the diagnosis based on DaTSCAN and will also validate the diagnosis based on the two tests with a clinical examination performed at least 1 year after the initial presentation as a surrogate gold standard diagnostic test.Ethics and dissemination: The local ethics commission (Health Research Authority East Midlands – Derby Research Ethics Committee) has approved this study (REC ref.: 16/EM/
Roussakis A-A, Towey D, Piccini P, 2017, LEVODOPA-INDUCED DYSKINESIAS IN PARKINSON'S: IMAGING OF STRIATAL DAT DENSITY OVER TIME, Publisher: BMJ PUBLISHING GROUP, Pages: A39-A39, ISSN: 0022-3050
Martin-Bastida A, Lao-Kaim NP, Xing Y, et al., 2017, NIGRAL IRON SUSCEPTIBILITY IN PARKINSON'S DISEASE: A LONGITUDINAL STUDY, Publisher: BMJ PUBLISHING GROUP, Pages: A34-A35, ISSN: 0022-3050
Politis M, Sauerbier A, Loane C, et al., 2017, Sustained striatal dopamine levels following intestinal levodopa infusions in Parkinson's disease patients, MOVEMENT DISORDERS, Vol: 32, Pages: 235-240, ISSN: 0885-3185
Li X, Xing Y, Martin-Bastida A, et al., 2017, Patterns of grey matter loss associated with motor subscores in early Parkinson's disease., NeuroImage: Clinical, Vol: 17, Pages: 498-504, ISSN: 2213-1582
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.
Lao-Kaim NP, Piccini P, Tai YF, 2017, Restorative strategies in movement disorders: the contribution of imaging, Current Neurology and Neuroscience Reports, Vol: 17, ISSN: 1528-4042
Purpose of ReviewThe purpose of this review was to review the imaging, particularly positron emission tomography (PET), findings in neurorestoration studies in movement disorders, with specific focus on neural transplantation in Parkinson’s disease (PD) and Huntington’s disease (HD).Recent FindingsPET findings in PD transplantation studies have shown that graft survival as reflected by increases in dopaminergic PET markers does not necessarily correlate with clinical improvement. PD patients with more denervated ventral striatum and more imbalanced serotonin-to-dopamine ratio in the grafted neurons tended to have worse outcome. In HD transplantation studies, variable graft survival and clinical responses may be related to host inflammatory/immune responses to the grafts.SummaryInformation gleaned from imaging findings in previous neural transplantation studies has been used to refine study protocol and patient selection in future trials. This includes identifying suitable candidates for transplantation using imaging markers, employing multiple and/or novel PET tracers to better assess graft functions and inflammatory responses to grafts.
Li W, Lao-Kaim N, Roussakis AA, et al., 2017, 11C-PE2I and 18F-DOPA PET for assessing progression rate in Parkinson’s: a longitudinal study, Movement Disorders, Vol: 33, Pages: 117-127, ISSN: 0885-3185
Background18F-dopa PET measuring aromatic l-amino acid decarboxylase activity is regarded as the gold standard for evaluating dopaminergic function in Parkinson's disease. Radioligands for dopamine transporters are also used in clinical trials and for confirming PD diagnosis. Currently, it is not clear which imaging marker is more reliable for assessing clinical severity and rate of progression. The objective of this study was to directly compare 18F-dopa with the highly selective dopamine transporter radioligand 11C-PE2I for the assessment of motor severity and rate of progression in PD.MethodsThirty-three mild-moderate PD patients underwent 18F-dopa and 11C-PE2I PET at baseline. Twenty-three were followed up for 18.8 ± 3.4 months.ResultsStandard multiple regression at baseline indicated that 11C-PE2I BPND predicted UPDRS-III and bradykinesia-rigidity scores (P < 0.05), whereas 18F-dopa Ki did not make significant unique explanatory contributions. Voxel-wise analysis showed negative correlations between 11C-PE2I BPND and motor severity across the whole striatum bilaterally. 18F-Dopa Ki clusters were restricted to the most affected putamen and caudate. Longitudinally, negative correlations were found between striatal Δ11C-PE2I BPND, ΔUPDRS-III, and Δbradykinesia-rigidity, whereas no significant associations were found for Δ18F-dopa Ki. One cluster in the most affected putamen was identified in the longitudinal voxel-wise analysis showing a negative relationship between Δ11C-PE2I BPND and Δbradykinesia-rigidity.ConclusionsStriatal 11C-PE2I appears to show greater sensitivity for detecting differences in motor severity than 18F-dopa. Furthermore, dopamine transporter decline is closely associated with motor progression over time, whereas no such relationship was found with aromatic l-amino acid decarboxylase. 11C-PE2I may be more effective for evaluating the efficacy of neuroprotective treatments in PD. © 2017 Interna
Li W, Lao-Kaim NP, Roussakis 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, 23rd World Congress of Neurology (WCN), Publisher: ELSEVIER SCIENCE BV, Pages: 128-128, ISSN: 0022-510X
Roussakis AA, Towey D, Piccini P, 2017, Longitudinal single-photon emitted computed tomography (SPECT) study of striatal dopamine transporter (DAT) density: Relevance to levodopa-induced dyskinesias in Parkinson's disease, 23rd World Congress of Neurology (WCN), Publisher: ELSEVIER SCIENCE BV, Pages: 949-949, ISSN: 0022-510X
Piccini P, 2017, Parkinson's disease and Huntington's disease by PET and MRI, 23rd World Congress of Neurology (WCN), Publisher: ELSEVIER SCIENCE BV, Pages: 21-22, ISSN: 0022-510X
Pietracupa S, Martin Bastida A, Piccini P, 2017, Iron metabolism and its detection through MRI in parkinsonian disorders: a systematic review., Neurological Sciences, ISSN: 1590-1874
Iron deposition in the brain normally increase with age, but its accumulation in certain regions is observed in a number of neurodegenerative diseases including Parkinson’s disease (PD) and other parkinsonisms. Whether iron overload leads to dopaminergic neuronal death in the SN of PD patients or is instead simply 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 visualization of basal ganglia is required. Deep gray matter nuclei are well presented in T2- and T2*-weighted images. 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 deposition in PD.
Politis M, Wilson H, Wu K, et al., 2017, Chronic exposure to dopamine agonists affects the integrity of striatal D2 receptors in Parkinson's patients., NeuroImage: Clinical, Vol: 16, Pages: 455-460, ISSN: 2213-1582
We aimed to investigate the integrity and clinical relevance of striatal dopamine receptor type-2 (D2R) availability in Parkinson's disease (PD) patients. We studied 68 PD patients, spanning from early to advanced disease stages, and 12 healthy controls. All participants received one [(11)C]raclopride PET scan in an OFF medication condition for quantification of striatal D2R availability in vivo. Parametric images of [(11)C]raclopride non-displaceable binding potential were generated from the dynamic [(11)C]raclopride scans using implementation of the simplified reference tissue model with cerebellum as the reference tissue. PET data were interrogated for correlations with clinical data related to disease burden and dopaminergic treatment. PD patients showed a mean 16.7% decrease in caudate D2R and a mean 3.5% increase in putaminal D2R availability compared to healthy controls. Lower caudate [(11)C]raclopride BPND correlated with longer PD duration. PD patients on dopamine agonist treatment had 9.2% reduced D2R availability in the caudate and 12.8% in the putamen compared to PD patients who never received treatment with dopamine agonists. Higher amounts of lifetime dopamine agonist therapy correlated with reduced D2Rs availability in both caudate and putamen. No associations between striatal D2R availability and levodopa treatment and dyskinesias were found. In advancing PD the caudate and putamen D2R availability are differentially affected. Chronic exposure to treatment with dopamine agonists, but no levodopa, suppresses striatal D2R availability, which may have relevance to output signaling to frontal lobes and the occurrence of executive deficits, but not dyskinesias.
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