Publications by authors named "Nicolas Carrière"

10 Publications

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Texture-based markers from structural imaging correlate with motor handicap in Parkinson's disease.

Sci Rep 2021 Feb 1;11(1):2724. Epub 2021 Feb 1.

Université de Lille, INSERM, U1172, CHU-Lille, Lille Neuroscience Cognition Research Centre, 1 place de Verdun, 59000, Lille, France.

There is a growing need for surrogate biomarkers for Parkinson's disease (PD). Structural analysis using magnetic resonance imaging with T1-weighted sequences has the potential to quantify histopathological changes. Degeneration is typically measured by the volume and shape of morphological changes. However, these changes appear late in the disease, preventing their use as surrogate markers. We investigated texture changes in 108 individuals, divided into three groups, matched in terms of sex and age: (1) healthy controls (n = 32); (2) patients with early-stage PD (n = 39); and (3) patients with late-stage PD and severe L-dopa-related complications (n = 37). All patients were assessed in off-treatment conditions. Statistical analysis of first- and second-order texture features was conducted in the substantia nigra, striatum, thalamus and sub-thalamic nucleus. Regions of interest volumetry and voxel-based morphometry were performed for comparison. Significantly different texture features were observed between the three populations, with some showing a gradual linear progression between the groups. The volumetric changes in the two PD patient groups were not significantly different. Texture features were significantly associated with clinical scores for motor handicap. These results suggest that texture features, measured in the nigrostriatal pathway at PD diagnosis, may be useful in predicting clinical progression of motor handicap.
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February 2021

Descriptive analysis of the French NS-Park registry: Towards a nation-wide Parkinson's disease cohort?

Parkinsonism Relat Disord 2019 07 25;64:226-234. Epub 2019 Apr 25.

Sorbonne Université, Assistance Publique Hôpitaux de Paris, Institut du Cerveau et de la Moelle épinière, ICM, Inserm U 1127, CNRS UMR 7225, Department of Neurology, Hôpital Pitié-Salpêtrière, F-75013, Paris, France; Center for Interdisciplinary Research in Biology, Collège de France, INSERM U1050, CNRS UMR7241, Labex Memolife, Paris Sciences et Lettres, Paris, France; AP-HP, Department of Neurology, Hôpital Avicenne, Hôpitaux Universitaires de Paris - Seine Saint Denis, Bobigny, France. Electronic address:

Introduction: Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's. The French clinical research network for PD (NS-Park) has created a national patient registry to i)report medical activity of Parkinson Expert Centers (PECs) to the Ministry of Health, ii)facilitate PD patients pre-screening for clinical trials, iii) provide a source for pharmaco-epidemiology studies.

Objective: Assess the French Parkinsonian population at a nation-wide level and discover new clinical characteristics.

Methods: In this feasibility study, PECs prospectively collected clinical data in a standardized manner. The population main clinical characteristics are described, focusing on motor and non-motor symptoms and treatments, assessing its representativeness. By using an unbiased clustering with multiple correspondence analysis (MCA), we also investigate potential relationships between multiple variables like symptoms and treatments, as clues for future studies.

Results: Between 2012 and 2016, among 11,157 included parkinsonian syndromes, 9454 (85%) had PD. MCA identified various profiles depending on disease duration. Occurrences of motor complications, axial signs, cognitive disorders and Levodopa use increase over time. Neurovegetative symptoms, psychiatric disorders, sleep disturbances and impulse control disorders (ICDs) seem stable over time. As expected, ICDs were associated to dopaminergic agonist use but other associations, such as ICDs and sleep disturbances for instance, or anxiety and depression, were found.

Conclusions: Our results report one of the biggest PD registries ever reported and demonstrate the feasibility of implementing a nation-wide registry of PD patients in France, a potent tool for future longitudinal studies and clinical trials' population selection, and for pharmaco-epidemiology and cost-effectiveness studies.
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July 2019

Whole-Brain High-Resolution Structural Connectome: Inter-Subject Validation and Application to the Anatomical Segmentation of the Striatum.

Brain Topogr 2017 May 7;30(3):291-302. Epub 2017 Feb 7.

Department of Neurology, Nancy University Hospital, Nancy, France.

The present study describes extraction of high-resolution structural connectome (HRSC) in 99 healthy subjects, acquired and made available by the Human Connectome Project. Single subject connectomes were then registered to the common surface space to allow assessment of inter-individual reproducibility of this novel technique using a leave-one-out approach. The anatomic relevance of the surface-based connectome was examined via a clustering algorithm, which identified anatomic subdivisions within the striatum. The connectivity of these striatal subdivisions were then mapped on the cortical and other subcortical surfaces. Findings demonstrate that HRSC analysis is robust across individuals and accurately models the actual underlying brain networks related to the striatum. This suggests that this method has the potential to model and characterize the healthy whole-brain structural network at high anatomic resolution.
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May 2017

Impulse Control Disorders in Parkinson's Disease are Associated with Alterations in Reward-Related Cortical Oscillations.

J Parkinsons Dis 2016 06;6(3):651-66

U1171, INSERM, Université de Lille, Lille, France.

Background: Impulse control disorders (ICDs) in Parkinson's disease (PD) are related to treatment with dopamine agonists, which is thought to deregulate the dopaminergic mesolimbic pathway and impair reward evaluation. EEG studies in healthy controls (HCs) have suggested that the increase in theta power observed after negative outcome is a marker of reward processing.

Objective: To compare outcome-locked, event-related spectral perturbation in a gambling task in PD patients with and without ICDs and in HCs.

Methods: Twelve PD patients with ICDs, 12 PD patients without ICDs and 14 HCs underwent EEG while performing a gambling task. The groups were compared in terms of (i) the peak EEG power in the theta (4-7 Hz), alpha (8-14 Hz) and beta (15-30 Hz) frequency bands between 200 and 500 ms after the outcome, and (ii) time-frequency plots at Fz, FCz and Cz.

Results: Positive outcomes were associated with greater theta power than negative outcomes in patients without ICDs and in HCs, but not in patients with ICDs. Patients with ICDs and HCs displayed greater theta power following unexpectedly high outcomes. HCs displayed greater beta power following high amplitude than low amplitude outcomes, whereas patients with ICD showed the opposite pattern.

Conclusions: In PD, ICDs are associated with (i) weaker modulation of frontocentral theta power by reward valence, (ii) greater frontocentral theta power following unexpected, high outcomes, and (iii) a reversal of the effect of risk on beta oscillations. These observations are consistent with an impairment in prediction error computation in the medial prefrontal cortex.
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June 2016

Magnetic Resonance Imaging Features of the Nigrostriatal System: Biomarkers of Parkinson's Disease Stages?

PLoS One 2016 1;11(4):e0147947. Epub 2016 Apr 1.

Department of Movement Disorders and Neurology, Lille University Hospital, Lille, France.

Introduction: Magnetic resonance imaging (MRI) can be used to identify biomarkers in Parkinson's disease (PD); R2* values reflect iron content related to high levels of oxidative stress, whereas volume and/or shape changes reflect neuronal death. We sought to assess iron overload in the nigrostriatal system and characterize its relationship with focal and overall atrophy of the striatum in the pivotal stages of PD.

Methods: Twenty controls and 70 PD patients at different disease stages (untreated de novo patients, treated early-stage patients and advanced-stage patients with L-dopa-related motor complications) were included in the study. We determined the R2* values in the substantia nigra, putamen and caudate nucleus, together with striatal volume and shape analysis. We also measured R2* in an acute MPTP mouse model and in a longitudinal follow-up two years later in the early-stage PD patients.

Results: The R2* values in the substantia nigra, putamen and caudate nucleus were significantly higher in de novo PD patients than in controls. Early-stage patients displayed significantly higher R2* values in the substantia nigra (with changes in striatal shape), relative to de novo patients. Measurements after a two-year follow-up in early-stage patients and characterization of the acute MPTP mouse model confirmed that R2* changed rapidly with disease progression. Advanced-stage patients displayed significant atrophy of striatum, relative to earlier disease stages.

Conclusion: Each pivotal stage in PD appears to be characterized by putative nigrostriatal MRI biomarkers: iron overload at the de novo stage, striatal shape changes at early-stage disease and generalized striatal atrophy at advanced disease.
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August 2016

Impaired corticostriatal connectivity in impulse control disorders in Parkinson disease.

Neurology 2015 May 29;84(21):2116-23. Epub 2015 Apr 29.

From the Université Lille Nord de France (N.C., R.L., L.D., C.D., K.D.), U1171, Lille; Service de Neurologie et Pathologie du Mouvement (N.C., L.D., K.D.) and Service de Neuroradiologie (R.L., C.D.), Centre Hospitalier Régional Universitaire, Lille, France.

Objectives: To compare the striatum's resting-state functional connectivity in patients with Parkinson disease (PD) with and without impulse control disorders (ICDs).

Methods: Twenty patients with PD and ICDs, 19 patients with PD but no ICDs, and 19 healthy controls underwent fMRI in the resting state. The ventral striatum, dorsal caudate, and anterior and posterior putamen were segmented semiautomatically. For each region of interest, a seed-based connectivity analysis was performed on preprocessed fMRI data mapped on the ipsilateral cortical surface. An additional cortical thickness analysis was used to assess and compare gray matter atrophy in the 3 study subgroups.

Results: The presence of an ICD in patients with PD was associated with functional disconnection between the left anterior putamen and both the left inferior temporal gyrus and the left anterior cingulate gyrus, as well as a trend toward a functional disconnection between several motor and associative striatal regions and limbic, associative, and motor cortical regions. Patients without ICDs did not differ from healthy controls in corticostriatal connectivity. The cortical thickness analysis did not reveal any significant differences among the 3 study subgroups.

Conclusions: In PD, ICDs are associated with altered connectivity between an associative striatal area (the left anterior putamen) and associative and limbic cortical regions (the left inferior temporal gyrus and the left anterior cingulate gyrus).
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May 2015

[Hypersexuality in Parkinson's disease. Advantage of the presence of the entourage for medical assessment].

Presse Med 2015 Mar 8;44(3):e51-8. Epub 2015 Jan 8.

CHRU de Lille, hôpital Fontan, service de psychiatrie adulte, 59037 Lille cedex, France; Université du Droit et de la Santé de Lille, EA 4559, 59000 Lille, France.

Objective: To improve the management of hypersexuality caused by antiparkinsonian treatment and its psychopathological implications in patients with Parkinson's disease (PD). If hypersexuality is a classic form of impulse control disorder (ICD) observed in PD, its rate is certainly underestimated.

Methods: We have proposed to meet patients with Parkinson's disease, referred by the neurology department of Lille University Hospital, for detection or suspicion of hypersexuality, in the presence of their spouse. The session consisted of an interview conducted by our psychiatry team. This evaluation was conducted between January 1 and August 31, 2011. Nine patients were referred to our service, 7 agreed to meet us, 6 of them with their spouse.

Results: An interview in the presence of the spouse has improved hypersexuality screening and information given to the patient and his close contacts regarding the side effects of treatment, and particularly the occurrence of hypersexuality. It also highlighted the various expressions of these behavioral changes, often minimized by patients, as spouses had great difficulty dealing with this. It helped them to improve verbal communication and, therefore, to be more informative concerning sexual behavior changes in connection with the treatment and its management. Finally, it has enabled improved support for secondary consequences of this impulse control disorder, such as guilt, jealousy or shame. Our interest has also focused on the impact of this hypersexuality on patients' families. Among the six sets partners, four had symptoms requiring specific psychiatric care: depression, suicidal intention or post-traumatic stress disorder.

Perspective: Hypersexuality seems underestimated in patients receiving antiparkinsonian treatment. This underestimation is probably linked to some defense mechanisms such as denial or minimization, but also to the feelings generated by these behavioral problems, such as shame or guilt. On the other hand, some patients do not experience stress related behavioral changes (even though the family may complain). Systematic partner interview could be a solution to improving this screening.
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March 2015

Apathy in Parkinson's disease is associated with nucleus accumbens atrophy: a magnetic resonance imaging shape analysis.

Mov Disord 2014 Jun 10;29(7):897-903. Epub 2014 May 10.

Service de Neurologie et Pathologie du Mouvement, Centre Hospitalier Régional Universitaire, Lille, France; Université Lille Nord de France, EA 1046, Lille, France.

Apathy is characterized by lack of interest, loss of initiative, and flattening of affect. It is a frequent, very disabling nonmotor complication of Parkinson's disease (PD). The condition may notably occur when dopaminergic medications are tapered after the initiation of subthalamic stimulation and thus can be referred to as "dopaminergic apathy." Even in the absence of tapering, some patients may develop a form of apathy as PD progresses. This form is often related to cognitive decline and does not respond to dopaminergic medications (dopa-resistant apathy). We aimed at determining whether dopa-resistant apathy in PD is related to striatofrontal morphological changes. We compared the shape of the striatum (using spherical harmonic parameterization and sampling in a three-dimensional point distribution model [SPHARM-PDM]), cortical thickness, and fractional anisotropy (using tract-based spatial statistics) in 10 consecutive patients with dopamine-refractory apathy, 10 matched nonapathetic PD patients and 10 healthy controls. Apathy in PD was associated with atrophy of the left nucleus accumbens. The SPHARM-PDM analysis highlighted (1) a positive correlation between the severity of apathy and atrophy of the left nucleus accumbens, (2) greater atrophy of the dorsolateral head of the left caudate in apathetic patients than in nonapathetic patients, and (3) greater atrophy in the bilateral nucleus accumbens in apathetic patients than in controls. There were no significant intergroup differences in cortical thickness or fractional anisotropy. Dopa-resistant apathy in PD was associated with atrophy of the left nucleus accumbens and the dorsolateral head of the left caudate.
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June 2014

Neurological picture. Acquired hepatocerebral degeneration revealed by neurogenic hyperventilation syndrome and myelitis.

J Neurol Neurosurg Psychiatry 2012 Oct 8;83(10):999-1000. Epub 2012 Jul 8.

University Lille Nord de France, UDSL, Lille, France.

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October 2012