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1. Quantitative brainstem and spinal MRI in amyotrophic lateral sclerosis: implications for predicting noninvasive ventilation needs

Author

Khamaysa, M., Lefort, M., Pélégrini-Issac, M., Lackmy-Vallée, A., Mendili, M. M. El, Preuilh, A., Devos, D., Bruneteau, G., Salachas, F., Lenglet, T., Amador, Md. M., Le Forestier, N., Hesters, A., Gonzalez, J., Rolland, A.-S., Desnuelle, C., Chupin, M., Querin, G., Georges, M., Morelot-Panzini, C., Marchand-Pauvert, V., and Pradat, P.-F.

Published
2024
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4. MAPT STUDY: A MULTIDOMAIN APPROACH FOR PREVENTING ALZHEIMER'S DISEASE: DESIGN AND BASELINE DATA.

Author

Vellas, B, Carrie, I, Gillette-Guyonnet, S, Touchon, J, Dantoine, T, Dartigues, JF, Cuffi, MN, Bordes, S, Gasnier, Y, Robert, P, Bories, L, Rouaud, O, Desclaux, F, Sudres, K, Bonnefoy, M, Pesce, A, Dufouil, C, Lehericy, S, Chupin, M, Mangin, JF, Payoux, P, Adel, D, Legrand, P, Catheline, D, Kanony, C, Zaim, M, Molinier, L, Costa, N, Delrieu, J, Voisin, T, Faisant, C, Lala, F, Nourhashémi, F, Rolland, Y, Van Kan, G Abellan, Dupuy, C, Cantet, C, Cestac, P, Belleville, S, Willis, S, Cesari, M, Weiner, MW, Soto, ME, Ousset, PJ, and Andrieu, S

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Alzheimer's Disease, Clinical Research, Neurodegenerative, Brain Disorders, Clinical Trials and Supportive Activities, Aging, Prevention, Behavioral and Social Science, Neurosciences, Nutrition, Acquired Cognitive Impairment, Dementia, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Complementary and Integrative Health, Neurological, Alzheimer’s disease, Multidomain intervention, Omega-3 fatty acids, Biological psychology, Cognitive and computational psychology
Abstract

ObjectiveThe Multidomain Alzheimer Preventive Trial (MAPT study) was designed to assess the efficacy of isolated supplementation with omega-3 fatty acid, an isolated multidomain intervention (consisting of nutritional counseling, physical exercise, cognitive stimulation) or a combination of the two interventions on the change of cognitive functions in frail subjects aged 70 years and older for a period of 3 years. Ancillary neuroimaging studies were additionally implemented to evaluate the impact of interventions on cerebral metabolism (FDG PET scans) and atrophy rate (MRIs), as well as brain amyloïd deposit (AV45 PET scans).Design patients1680 subjects (mean age: 75.3 years; female: 64.8 %), enrolled by 13 memory clinics, were randomized into one of the following four groups: omega-3 supplementation alone, multidomain intervention alone, omega-3 plus multidomain intervention, or placebo. Participants underwent cognitive, functional and biological assessments at M6, M12, M24 and M36 visits. The primary endpoint is a change of memory function at 3 years, as assessed by the Free and Cued Selective Reminding test. All participants will be followed for 2 additional years after the 3-years intervention (MAPT PLUS extension study).Interventions1/Omega-3 supplementation: two soft capsules daily as a single dose, containing a total of 400 mg docosahexaenoic acid (DHA), i.e., 800 mg docosahexaenoic acid per day, for 3 years. 2/ Multidomain intervention: collective training sessions conducted in small groups (6-8 participants) in twelve 120-minute sessions over the first 2 months (two sessions a week for the first month, and one session a week the second month) then a 60-minute session per month in the following three areas: nutrition, physical activity, and cognition until the end of the 3 years. In addition to the collective sessions, individualized preventive outpatient visits exploring possible risk factors for cognitive decline are performed at baseline, M12 and M24.Baseline populationFor cognition, the mean MMSE at baseline was 28.1 (± 1.6). About 58% and 42% of participants had a CDR score equal to 0 and 0.5, respectively. Regarding mobility status, 200 (11.9%) had a 4-m gait speed lower or equal to 0.8 m/s. According to the Fried criteria, 673 (42.1%) participants were considered pre frail, and 51 (3.2%) frail. The red blood cell DHA content was 26.1 ± 8.1 µg/g. Five hundred and three participants underwent baseline MRI. AV45 PET scans were performed in 271 individuals and preliminary results showed that 38.0% had a cortical SUVR > 1.17, which gave an indication of significant brain amyloïd deposit. DISCUSSION: The MAPT trial is presently the first largest and longest multidomain preventive trial relevant to cognitive decline in older adults with subjective memory complaints. The multidomain intervention designed for the MAPT trial is likely to be easily implemented within the general population.

Published
2014

8. Trial of Deferiprone in Parkinson's Disease

Author

Devos, D., Labreuche, J., Rascol, O., Corvol, J.C., Duhamel, A., Delannoy, P. Guyon, Poewe, W., Compta, Y., Pavese, N., Růžička, E., Dušek, P., Post, B., Bloem, B.R., Berg, D., Maetzler, W., Otto, M., Habert, M.O., Lehericy, S., Ferreira, J., Dodel, R., Tranchant, C., Eusebio, A., Thobois, S., Marques, A.R., Meissner, W.G., Ory-Magne, F., Walter, U., Bie, R.M. de, Gago, M., Vilas, D., Kulisevsky, J., Januario, C., Coelho, M.V.S., Behnke, S., Worth, P., Seppi, K., Ouk, T., Potey, C., Leclercq, C., Viard, R., Kuchcinski, G., Lopes, R., Pruvo, J.P., Pigny, P., Garçon, G., Simonin, O., Carpentier, J., Rolland, A.S., Nyholm, D., Scherfler, C., Mangin, J.F., Chupin, M., Bordet, R., Dexter, D.T., Fradette, C., Spino, M., Tricta, F., Ayton, S., Bush, A.I., Devedjian, J.C., Duce, J.A., Cabantchik, I., Defebvre, L., Deplanque, D., Moreau, C., Devos, D., Labreuche, J., Rascol, O., Corvol, J.C., Duhamel, A., Delannoy, P. Guyon, Poewe, W., Compta, Y., Pavese, N., Růžička, E., Dušek, P., Post, B., Bloem, B.R., Berg, D., Maetzler, W., Otto, M., Habert, M.O., Lehericy, S., Ferreira, J., Dodel, R., Tranchant, C., Eusebio, A., Thobois, S., Marques, A.R., Meissner, W.G., Ory-Magne, F., Walter, U., Bie, R.M. de, Gago, M., Vilas, D., Kulisevsky, J., Januario, C., Coelho, M.V.S., Behnke, S., Worth, P., Seppi, K., Ouk, T., Potey, C., Leclercq, C., Viard, R., Kuchcinski, G., Lopes, R., Pruvo, J.P., Pigny, P., Garçon, G., Simonin, O., Carpentier, J., Rolland, A.S., Nyholm, D., Scherfler, C., Mangin, J.F., Chupin, M., Bordet, R., Dexter, D.T., Fradette, C., Spino, M., Tricta, F., Ayton, S., Bush, A.I., Devedjian, J.C., Duce, J.A., Cabantchik, I., Defebvre, L., Deplanque, D., and Moreau, C.

Abstract

Item does not contain fulltext, BACKGROUND: Iron content is increased in the substantia nigra of persons with Parkinson's disease and may contribute to the pathophysiology of the disorder. Early research suggests that the iron chelator deferiprone can reduce nigrostriatal iron content in persons with Parkinson's disease, but its effects on disease progression are unclear. METHODS: We conducted a multicenter, phase 2, randomized, double-blind trial involving participants with newly diagnosed Parkinson's disease who had never received levodopa. Participants were assigned (in a 1:1 ratio) to receive oral deferiprone at a dose of 15 mg per kilogram of body weight twice daily or matched placebo for 36 weeks. Dopaminergic therapy was withheld unless deemed necessary for symptom control. The primary outcome was the change in the total score on the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS; range, 0 to 260, with higher scores indicating more severe impairment) at 36 weeks. Secondary and exploratory clinical outcomes at up to 40 weeks included measures of motor and nonmotor disability. Brain iron content measured with the use of magnetic resonance imaging was also an exploratory outcome. RESULTS: A total of 372 participants were enrolled; 186 were assigned to receive deferiprone and 186 to receive placebo. Progression of symptoms led to the initiation of dopaminergic therapy in 22.0% of the participants in the deferiprone group and 2.7% of those in the placebo group. The mean MDS-UPDRS total score at baseline was 34.3 in the deferiprone group and 33.2 in the placebo group and increased (worsened) by 15.6 points and 6.3 points, respectively (difference, 9.3 points; 95% confidence interval, 6.3 to 12.2; P<0.001). Nigrostriatal iron content decreased more in the deferiprone group than in the placebo group. The main serious adverse events with deferiprone were agranulocytosis in 2 participants and neutropenia in 3 participants. CONCLUSIONS: In parti

Published
2022

16. Relations between C9orf72 expansion size in blood, age at onset, age at collection and transmission across generations in patients and presymptomatic carriers

Author

Fournier, C., Barbier, M., Camuzat, A., Anquetil, V., Lattante, Serena, Clot, F., Cazeneuve, C., Rinaldi, D., Couratier, P., Deramecourt, V., Sabatelli, Mario, Belliard, S., Vercelletto, M., Forlani, S., Jornea, L., Brice, A., Auriacombe, S., Blanc, F., Bouteleau-Bretonniere, C., Ceccaldi, M., Didic, M., Dubois, B., Duyckaerts, C., Etcharry-Bouix, F., Golfier, V., Hannequin, D., Lacomblez, L., Le Ber, I., Levy, R., Michel, B. -F., Pasquier, F., Thomas-Anterion, C., Pariente, J., Sellal, F., Benchetrit, E., Bertin, H., Bertrand, A., Bissery, A., Bombois, S., Boncoeur, M. -P., Cassagnaud, P., Chastan, M., Chen, Y., Chupin, M., Colliot, O., Delbeucq, X., Delmaire, C., Gerardin, E., Hossein-Foucher, C., Habert, M. -O., Lautrette, G., Lebouvier, T., Lehericy, S., Le Toullec, B., Martineau, K., Mackowiak, M. -A., Monteil, J., Petyt, G., Pradat, P. -F., Oya, A. -H., Rollin-Sillaire, A., Salachas, F., Sayah, S., Wallon, D., Leguern, E., Lattante S. (ORCID:0000-0003-2891-0340), Sabatelli M. (ORCID:0000-0001-6635-4985), Fournier, C., Barbier, M., Camuzat, A., Anquetil, V., Lattante, Serena, Clot, F., Cazeneuve, C., Rinaldi, D., Couratier, P., Deramecourt, V., Sabatelli, Mario, Belliard, S., Vercelletto, M., Forlani, S., Jornea, L., Brice, A., Auriacombe, S., Blanc, F., Bouteleau-Bretonniere, C., Ceccaldi, M., Didic, M., Dubois, B., Duyckaerts, C., Etcharry-Bouix, F., Golfier, V., Hannequin, D., Lacomblez, L., Le Ber, I., Levy, R., Michel, B. -F., Pasquier, F., Thomas-Anterion, C., Pariente, J., Sellal, F., Benchetrit, E., Bertin, H., Bertrand, A., Bissery, A., Bombois, S., Boncoeur, M. -P., Cassagnaud, P., Chastan, M., Chen, Y., Chupin, M., Colliot, O., Delbeucq, X., Delmaire, C., Gerardin, E., Hossein-Foucher, C., Habert, M. -O., Lautrette, G., Lebouvier, T., Lehericy, S., Le Toullec, B., Martineau, K., Mackowiak, M. -A., Monteil, J., Petyt, G., Pradat, P. -F., Oya, A. -H., Rollin-Sillaire, A., Salachas, F., Sayah, S., Wallon, D., Leguern, E., Lattante S. (ORCID:0000-0003-2891-0340), and Sabatelli M. (ORCID:0000-0001-6635-4985)

Abstract

A (GGGGCC) n repeat expansion in C9orf72 gene is the major cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). The relations between the repeats size and the age at disease onset (AO) or the clinical phenotype (FTD vs. ALS) were investigated in 125 FTD, ALS, and presymptomatic carriers. Positive correlations were found between repeats number and the AO (p < 10 e−4 ) but our results suggested that the association was mainly driven by age at collection (p < 10 e−4 ). A weaker association was observed with clinical presentation (p = 0.02), which became nonsignificant after adjustment for the age at collection in each group. Importantly, repeats number variably expanded or contracted over time in carriers with multiple blood samples, as well as through generations in parent-offspring pairs, conversely to what occurs in several expansion diseases with anticipation at the molecular level. Finally, this study establishes that measure of repeats number in lymphocytes is not a reliable biomarker predictive of the AO or disease outcome in C9orf72 long expansion carriers.

Published
2019

17. MAPT STUDY: A MULTIDOMAIN APPROACH FOR PREVENTING ALZHEIMER'S DISEASE: DESIGN AND BASELINE DATA

Author

Vellas, B, Carrie, I, Gillette-Guyonnet, S, Touchon, J, Dantoine, T, Dartigues, JF, Cuffi, MN, Bordes, S, Gasnier, Y, Robert, P, Bories, L, Rouaud, O, Desclaux, F, Sudres, K, Bonnefoy, M, Pesce, A, Dufouil, C, Lehericy, S, Chupin, M, Mangin, JF, Payoux, P, Adel, D, Legrand, P, Catheline, D, Kanony, C, Zaim, M, Molinier, L, Costa, N, Delrieu, J, Voisin, T, Faisant, C, Lala, F, Nourhashémi, F, Rolland, Y, Van Kan, G Abellan, Dupuy, C, Cantet, C, Cestac, P, Belleville, S, Willis, S, Cesari, M, Weiner, MW, Soto, ME, Ousset, PJ, and Andrieu, S

Subjects
Aging, Multidomain intervention, Prevention, Clinical Trials and Supportive Activities, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurodegenerative, Alzheimer's Disease, Article, Brain Disorders, Clinical Research, Complementary and Integrative Health, Behavioral and Social Science, Neurological, Omega-3 fatty acids, Acquired Cognitive Impairment, Dementia, Alzheimer’s disease, Nutrition
Abstract

ObjectiveThe Multidomain Alzheimer Preventive Trial (MAPT study) was designed to assess the efficacy of isolated supplementation with omega-3 fatty acid, an isolated multidomain intervention (consisting of nutritional counseling, physical exercise, cognitive stimulation) or a combination of the two interventions on the change of cognitive functions in frail subjects aged 70 years and older for a period of 3 years. Ancillary neuroimaging studies were additionally implemented to evaluate the impact of interventions on cerebral metabolism (FDG PET scans) and atrophy rate (MRIs), as well as brain amyloïd deposit (AV45 PET scans).Design patients1680 subjects (mean age: 75.3 years; female: 64.8 %), enrolled by 13 memory clinics, were randomized into one of the following four groups: omega-3 supplementation alone, multidomain intervention alone, omega-3 plus multidomain intervention, or placebo. Participants underwent cognitive, functional and biological assessments at M6, M12, M24 and M36 visits. The primary endpoint is a change of memory function at 3 years, as assessed by the Free and Cued Selective Reminding test. All participants will be followed for 2 additional years after the 3-years intervention (MAPT PLUS extension study).Interventions1/Omega-3 supplementation: two soft capsules daily as a single dose, containing a total of 400 mg docosahexaenoic acid (DHA), i.e., 800 mg docosahexaenoic acid per day, for 3 years. 2/ Multidomain intervention: collective training sessions conducted in small groups (6-8 participants) in twelve 120-minute sessions over the first 2 months (two sessions a week for the first month, and one session a week the second month) then a 60-minute session per month in the following three areas: nutrition, physical activity, and cognition until the end of the 3 years. In addition to the collective sessions, individualized preventive outpatient visits exploring possible risk factors for cognitive decline are performed at baseline, M12 and M24.Baseline populationFor cognition, the mean MMSE at baseline was 28.1 (± 1.6). About 58% and 42% of participants had a CDR score equal to 0 and 0.5, respectively. Regarding mobility status, 200 (11.9%) had a 4-m gait speed lower or equal to 0.8 m/s. According to the Fried criteria, 673 (42.1%) participants were considered pre frail, and 51 (3.2%) frail. The red blood cell DHA content was 26.1 ± 8.1 µg/g. Five hundred and three participants underwent baseline MRI. AV45 PET scans were performed in 271 individuals and preliminary results showed that 38.0% had a cortical SUVR > 1.17, which gave an indication of significant brain amyloïd deposit. DISCUSSION: The MAPT trial is presently the first largest and longest multidomain preventive trial relevant to cognitive decline in older adults with subjective memory complaints. The multidomain intervention designed for the MAPT trial is likely to be easily implemented within the general population.

Published
2015

22. Brain networks in posterior cortical atrophy: A single case tractography study and literature review

Author

Migliaccio, Raffaella, Agosta, F, Toba, Mn, Samri, D, Corlier, F, De Souza, Lc, Chupin, M, Sharman, M, Gorno Tempini, Ml, Dubois, B, Filippi, M, Bartolomeo, Paolo, Migliaccio, Raffaella, Agosta, F, Toba, Mn, Samri, D, Corlier, F, De Souza, Lc, Chupin, M, Sharman, M, Gorno Tempini, Ml, Dubois, B, Filippi, M, and Bartolomeo, Paolo

Abstract

Posterior cortical atrophy (PCA) is rare neurodegenerative dementia, clinically characterized by a progressive decline in higher-visual object and space processing. After a brief review of the literature on the neuroimaging in PCA, here we present a study of the brain structural connectivity in a patient with PCA and progressive isolated visual and visuo-motor signs. Clinical and cognitive data were acquired in a 58-years-old patient (woman, right-handed, disease duration 18 months). Brain structural and diffusion tensor (DT) Magnetic Resonance Imaging (MRI) were obtained. A voxel-based morphometry (VBM) study was performed to explore the pattern of gray matter (GM) atrophy, and a fully automatic segmentation was assessed to obtain the hippocampal volumes. DT MRI-based tractography was used to assess the integrity of long-range white matter (WM) pathways in the patient and in six sex- and age-matched healthy subjects. This PCA patient had a clinical syndrome characterized by left visual neglect, optic ataxia, and left limb apraxia, as well as mild visuo-spatial episodic memory impairment. VBM study showed bilateral posterior GM atrophy with right predominance; DT MRI tractography demonstrated WM damage to the right hemisphere only, including the superior and inferior longitudinal fasciculi and the inferior fronto-occipital fasciculus, as compared to age-matched controls. The homologous left-hemisphere tracts were spared. No difference was found between left and right hippocampal volumes. These data suggest that selective visuo-spatial deficits typical of PCA might not result from cortical damage alone, but by a right-lateralized network-level dysfunction including WM damage along the major visual pathways.

Published
2011

38. Psychometric Study of Praxilene

Author

Bouvier, J B, Passeron, O, and Chupin, M P

Abstract

Naftidrofuryl (Praxilene) has been shown experimentally to improve the metabolism of brain cells where this has been impaired by advancing ischaemia due to arteriosclerosis. It has been evaluated in warded chronic patients showing signs of impaired intellectual ability. The trial was performed double-blind involving an identical placebo and the results assessed using psychometric tests and analyzed statistically. The results confirm the effectiveness of Naftidrofuryl (Praxilene) in improving intellectual performance and this was particularly apparent in the less severely affected.

Published
1974
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39. Adrenocortical function in idiopathic haemochromatosis

Author

Charbonnel, B., Chupin, M., Lucas, B., Chupin, F., and Guillon, J.

Abstract

In idiopathic haemochromatosis, excessive iron deposits include adrenal cortex, and mainly the zona glomerulosa. In this view, we measured basal and poststimulative values of plasma cortisol, aldosterone and renin activity (RA) in two groups of patients: 1) 9 normal-salt repleted subjects (NSR) who were subjected to iv ACTH and furosemide tests, 2) 10 patients who were subjected to chronic salt depletion (CSD), to iv ACTH and furosemide tests. The results were compared with two groups of 7 healthy volunteers (NSR and CSD). In the patients, basal cortisol values were either normal or increased in cases of poorly controlled diabetes (21 ± 2.1 μg/100 ml, P< 0.01) and cortisol increase after ACTH injection was normal (to 43.3 ± 4.3 μg/100ml). In the 9 NSR patients, basal aldosterone (7.75 ± 1.5 ng/100 ml) and RA (1.55 ± 0.27 ng/ml/h) values were normal; aldosterone and RA rose after furosemide injection: these increases were similar in these patients (respectively to: 13.5 ± 2.2 ng/100 ml and 4.3 ± 0.6 ng/ml/h) and in the 7 NSR controls. In the 10 CSD patients, basal aldosterone and RA values were always increased (26.5 ± 3.2 ng/100 ml and 8.5 ± 2.3 ng/ml/h) as much as in the 7 CSD controls. After ACTH administration, aldosterone values (26.1 ± 4 in NSR patients, 54 ± 8 ng/100 ml in CSD patients) were the same as in the two control groups. This study suggests that there is no adrenocortical deficiency in idiopathic haemochromatosis, in spite of excessive iron deposits in the adrenal cortex.

Published
1980
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40. Pituitary function in idiopathic haemochromatosis: hormonal study in 36 male patients

Author

Charbonnel, B., Chupin, M., Le Grand, A., and Guillon, J.

Abstract

Thirty-six male patients with idiopathic haemochromatosis were subjected to measurements of basal plasma values of testosterone, LH and FSH and to an LRH test. Nineteen were also subjected to basal plasma determinations of T3, T4, cortisol, TSH and prolactin and to a TRH test. In 11 cases GH values were measured before, during and after an arginine infusion.Seventeen patients were found to have low levels of testosterone, LH and FSH, and no gonadotrophin responses to LRH. Seventeen others had normal levels of these three hormones, with normal responses to LRH. The two remaining patients had normal testosterone values but very increased gonadotrophin values: a fact which remains unexplained.Basal levels of prolactin, GH, T3, T4, and TSH were normal: cortisol levels were either normal or increased in cases of poorly controlled diabetes. Prolactin responses to TRH were always normal. TSH responses to TRH were impaired in 2 cases, and GH responses to arginine in 3 cases.Considering that other factors may be involved in the few impairments found in TSH and GH stimulations, it is concluded that the only indisputable pituitary insufficiency in about half of the cases of idiopathic haemochromatosis is gonadotrophic.

Published
1981
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41. The Cortical Lesion Pattern Of Dysexecutive Syndrome in MEMENTO cohort

Author

Andriuta, D., Roussel, M., Dufouil, C., Chene, G., Fischer, C., Azouani, C., Chupin, M., Dubois, B., Vellas, B., Florence Pasquier, Tison, F., Blanc, F., Godefroy, O., DESSAIVRE, Louise, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d’information Médicale [CHU de Bordeaux] (Pôle de Santé Publique), CHU Bordeaux [Bordeaux], Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Mémoire [CHU de Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Roger Salengro [Lille], Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), and CHU Strasbourg

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

International audience; Objective: The objective of this study was to investigate the association between cortical thickness and executive functions in the Memento Cohort.Background: Dysexecutive disorders are one early sign of Alzheimer’s disease (AD). Their precise cortical lesion patterns still remain undetermined. Memento cohort is a large French cohort with extensive clinical, neuropsychological and neuroimaging data for studying the natural history of AD in a large group of participants with different subtypes of mild cognitive impairment or isolated subjective cognitive complaints.Design/Methods: We selected from the Memento cohort (Dufouil et al., 2017) all subjects with available region of interest (ROI) cortical thickness data and executive function (verbal fluency and trail making test (TMT)) assessment (n=1924 out of N=2323). Mean MMSE was 28.02 (±1.6), 59.8 % of participants had a Clinical Dementia Rating scale of 0.5, 62.1 % were women. Stepwise linear regression adjusted on age, and education level were achieved to determine reduced brain parenchymal fraction (BPF) and decrease of cortical thickness regions related to both verbal fluency (literal and semantic) and time difference of TMT part B and part A performance (TMTB-At).Results: Semantic fluency was related to BPF and cortical thickness of right supramarginal, right cingulate isthmic and left entorhinal regions (R$^2$=0.133, p=0.0001). Literal fluency was related to BPF and cortical thickness of left pars orbitalis region (R$^2$=0.162, p=0. 0001). TMTB-At was related to cortical thickness of right precuneus and right isthmic cingulate regions (R$^2$=0.142, p=0.0001).Conclusions: The cortical lesion pattern of executive functions was the right supramarginal, right cingulate isthmic, left entorhinal regions, left pars orbitalis and right precuneus. To our knowledge this is the first study to determine precisely, from a large cohort with standardized assessments, the cortical regions related to executive performance.

42. [Eosinophilic fasciitis and Hodgkin's disease]

Author

Rodat O, Jl, Harousseau, Reynaud C, Noel Milpied, Jf, Stalder, and Chupin M

Subjects
Eosinophilia, Humans, Female, Fasciitis, Hodgkin Disease, Aged
Abstract

A case of eosinophilic fasciitis (EF) associated with Hodgkin disease is described. In eight previously published cases, EF was associated with immunologic diseases, such as autoimmune marrow aplasia. The relation between EF and Hodgkin disease should be studied by investigating the physiopathologic meaning of eosinophils in both conditions.

45. Modernization of hardware and data processing methods of a coercive spectrometer

Author

Chupin M., Latypov R., Isaeva A., Mukhametzyanov F., Davydov Y., Makridin A., Popov M., Chupin M., Latypov R., Isaeva A., Mukhametzyanov F., Davydov Y., Makridin A., and Popov M.

Abstract

© 2019 IEEE. The main aims of this project are modernization of control system and data acquisition block of coercive spectrometer based on modern analog and digital elements. Control system upgrade leads to improvement of signal detection quality and increase of signal-to-noise ratio. After modernization, system operator's work became simpler. Receiving and data processing complex became fully automatic.

48. Automatic segmentation of white matter hyperintensities robust to multicentre acquisition and pathological variability

Author

Samaille, T., Colliot, O., Cuingnet, R., Jouvent, E., Chabriat, H., Dormont, D., and Chupin, M.

Abstract

White matter hyperintensities (WMH), commonly seen on FLAIR images in elderly people, are a risk factor for dementia onset and have been associated with motor and cognitive deficits. We present here a method to fully automatically segment WMH from T1 and FLAIR images. Iterative steps of non linear diffusion followed by watershed segmentation were applied on FLAIR images until convergence. Diffusivity function and associated contrast parameter were carefully designed to adapt to WMH segmentation. It resulted in piecewise constant images with enhanced contrast between lesions and surrounding tissues. Selection of WMH areas was based on two characteristics: 1) a threshold automatically computed for intensity selection, 2) main location of areas in white matter. False positive areas were finally removed based on their proximity with cerebrospinal fluid/grey matter interface. Evaluation was performed on 67 patients: 24 with amnestic mild cognitive impairment (MCI), from five different centres, and 43 with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoaraiosis (CADASIL) acquired in a single centre. Results showed excellent volume agreement with manual delineation (Pearson coefficient: r=0.97, p<0.001) and substantial spatial correspondence (Similarity Index: 72%±16%). Our method appeared robust to acquisition differences across the centres as well as to pathological variability.

Published
2012
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49. Brain networks in posterior cortical atrophy: a single case tractography study and literature review

Author

Michael Sharman, Massimo Filippi, Raffaella Migliaccio, Federica Agosta, Leonardo Cruz de Souza, Bruno Dubois, Maria Luisa Gorno-Tempini, Paolo Bartolomeo, Marie Chupin, D. Samri, Fabian Corlier, Monica N. Toba, Center for Nanotechnology Innovation, @NEST (CNI), National Enterprise for nanoScience and nanoTechnology (NEST), Scuola Normale Superiore di Pisa (SNS)-Scuola Universitaria Superiore Sant'Anna [Pisa] (SSSUP)-Istituto Italiano di Tecnologia (IIT)-Consiglio Nazionale delle Ricerche [Pisa] (CNR PISA)-Scuola Normale Superiore di Pisa (SNS)-Scuola Universitaria Superiore Sant'Anna [Pisa] (SSSUP)-Istituto Italiano di Tecnologia (IIT)-Consiglio Nazionale delle Ricerche [Pisa] (CNR PISA), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University Hospital San Raffaele, Fédération de neurologie 4, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Migliaccio, R, Agosta, F, Toba, Mn, Samri, D, Corlier, F, de Souza, Lc, Chupin, M, Sharman, M, Gorno-Tempini, Ml, Dubois, B, Filippi, M, and Bartolomeo, P

Subjects
genetic structures, Cognitive Neuroscience, Experimental and Cognitive Psychology, Apraxia, Article, 050105 experimental psychology, White matter, 03 medical and health sciences, 0302 clinical medicine, Atrophy, Neuroimaging, Image Processing, Computer-Assisted, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, 0501 psychology and cognitive sciences, Brain Mapping, medicine.diagnostic_test, 05 social sciences, Brain, Posterior cortical atrophy, Magnetic resonance imaging, Anatomy, Middle Aged, medicine.disease, Diffusion Magnetic Resonance Imaging, Diffusion Tensor Imaging, Neuropsychology and Physiological Psychology, medicine.anatomical_structure, Female, Nerve Net, Psychology, Neuroscience, 030217 neurology & neurosurgery, Diffusion MRI, Tractography
Abstract

International audience; Posterior cortical atrophy (PCA) is rare neurodegenerative dementia, clinically characterized by a progressive decline in higher-visual object and space processing. After a brief review of the literature on the neuroimaging in PCA, here we present a study of the brain structural connectivity in a patient with PCA and progressive isolated visual and visuo-motor signs. Clinical and cognitive data were acquired in a 58-years-old patient (woman, right-handed, disease duration 18 months). Brain structural and diffusion tensor (DT) magnetic resonance imaging (MRI) were obtained. A voxel-based morphometry (VBM) study was performed to explore the pattern of gray matter (GM) atrophy, and a fully automatic segmentation was assessed to obtain the hippocampal volumes. DT MRI-based tractography was used to assess the integrity of long-range white matter (WM) pathways in the patient and in six sex- and age-matched healthy subjects. This PCA patient had a clinical syndrome characterized by left visual neglect, optic ataxia, and left limb apraxia, as well as mild visuo-spatial episodic memory impairment. VBM study showed bilateral posterior GM atrophy with right predominance; DT MRI tractography demonstrated WM damage to the right hemisphere only, including the superior and inferior longitudinal fasciculi and the inferior fronto-occipital fasciculus, as compared to age-matched controls. The homologous left-hemisphere tracts were spared. No difference was found between left and right hippocampal volumes. These data suggest that selective visuo-spatial deficits typical of PCA might not result from cortical damage alone, but by a right-lateralized network-level dysfunction including WM damage along the major visual pathways.

Published
2012

50. Longitudinal Changes of Clinical, Imaging, and Fluid Biomarkers in Preataxic and Early Ataxic Spinocerebellar Ataxia Type 2 and 7 Carriers.

Author

Coarelli G, Dubec-Fleury C, Petit E, Sayah S, Fischer C, Nassisi M, Gatignol P, Dorgham K, Daghsen L, Daye P, Cunha P, Kacher R, Hilab R, Hurmic H, Lamazière A, Lamy JC, Welter ML, Chupin M, Mangin JF, Lane R, Gaymard B, Pouget P, Audo I, Brice A, Tezenas du Montcel S, and Durr A

Subjects
Humans, Male, Female, Middle Aged, Adult, Longitudinal Studies, Heterozygote, Ataxin-7 genetics, Ataxin-2 genetics, Disease Progression, Brain diagnostic imaging, Spinocerebellar Ataxias diagnostic imaging, Spinocerebellar Ataxias genetics, Biomarkers blood, Magnetic Resonance Imaging, Neurofilament Proteins blood
Abstract

Background and Objectives: Brain MRI abnormalities and increases in neurofilament light chain (NfL) have mostly been observed in cross-sectional studies before ataxia onset in polyglutamine spinocerebellar ataxias. Our study aimed to identify longitudinal changes in biological, clinical, and/or imaging biomarkers in spinocerebellar ataxia (SCA) 2 and SCA7 carriers over 1 year., Methods: We studied SCA2 and SCA7 carriers and controls (expansion-negative relatives) at the Paris Brain Institute. Inclusion criteria included Scale for the Assessment and Rating of Ataxia (SARA) scores between 0 and 15. Assessments at baseline, 6 months, and 12 months comprised neurologic, quality of life, orofacial motor, neuropsychological, and ophthalmologic examinations, along with gait and oculomotor recordings, brain MRI, CSF, and blood sampling. The primary outcome was the longitudinal change in these assessments over 1 year., Results: We included 15 SCA2 carriers, 15 SCA7 carriers, and 10 controls between May 2020 and April 2021. At baseline, the ages were similar (41 [37, 46] for SCA2, 38 [28.5, 39.8] for SCA7, and 39.5 [31, 54.5] for controls, p = 0.78), as well the sex ( p = 0.61); SARA scores were low but different (4 [1.25, 6.5] in SCA2, 2 [0, 11.5] in SCA7, and 0 in controls, p < 0.01). Pons and medulla volumes were smaller in SCAs ( p < 0.05) and cerebellum volume only in SCA2 ( p = 0.01). Plasma NfL levels were higher in SCA participants (SCA2: 14.2 pg/mL [11.52, 15.89], SCA7: 15.53 [13.27, 23.23]) than in controls (4.88 [3.56, 6.17], p < 0.001). After 1-year follow-up, in SCA2, there was significant pons (-144 ± 60 mm 3 ) and cerebellum (-1,508 ± 580 mm 3 ) volume loss and a worsening of gait assessment; in SCA7, SARA score significantly increased (+1.3 ± 0.4) and outer retinal nuclear layer thickness decreased (-15.4 ± 1.6 μm); for both SCA groups, the orofacial motor assessment significantly worsened. For preataxic and early ataxic carriers, the strongest longitudinal deterioration on outcome measures was orofacial motility in SCA2 and retinal thickness in SCA7., Discussion: Despite the limitation of the small sample size, we detected annual changes in preataxic and early ataxic SCA individuals across brain MRI imaging, clinical scores, gait parameters, and retinal thickness. These parameters could serve as potential end points for future therapeutic trials in the preataxic phase., Trial Registration Information: ClinicalTrials.gov NCT04288128.

Published
2024
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