523 results on '"Thobois, S."'
Search Results
102. PET and SPECT functional imaging studies in Parkinsonian syndromes: from the lesion to its consequences
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Thobois, S., primary, Jahanshahi, M., additional, Pinto, S., additional, Frackowiak, R., additional, and Limousin-Dowsey, P., additional
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- 2004
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103. Anévrysme de la carotide interne intra-caverneuse compliquant une sinusite sphénoïdale
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Philippeau, F., primary, Hernette, D., additional, Thobois, S., additional, Turjman, F., additional, Bret, P., additional, Broussolle, E., additional, and Chazot, G., additional
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- 2004
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104. Traitement par stimulation pallidale continue des dyskinésies tardives provoquées par les neuroleptiques : résultats préliminaires d’une étude pilote multicentrique du groupe STARDYS
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Damier, Ph., primary, Thobois, S., additional, Witjas, T., additional, Derkinderen, P., additional, Xié, J., additional, Azulay, J. Ph., additional, Broussolle, E., additional, Burbaud, P., additional, Durif, F., additional, and Rascol, O., additional
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- 2004
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105. Chorea after Cardiopulmonary Bypass
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Thobois, S., primary, Bozio, A., additional, Ninet, J., additional, Akhavi, A., additional, and Broussolle, E., additional
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- 2004
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106. Mouvements anormaux de l'enfant
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Roubertie, A., Thobois, S., de Saint Martin, A., Billette de Villemeur, T., and Doummar, D.
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- 2006
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107. The Timing of Antiparkinsonian Treatment Reduction after Subthalamic Nucleus Stimulation
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Thobois, S., primary, Corvaisier, S., additional, Mertens, P., additional, Di Guardo, C., additional, Mollion, H., additional, Guenot, M., additional, Rochefort, F., additional, Chazot, G., additional, Sindou, M., additional, and Broussolle, E., additional
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- 2002
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108. Encéphalomyopathie mitochondriale de type Melas associée à un syndrome de Fahr avec calcifications cérébelleuses
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Younes-Mhenni, S, primary, Thobois, S, additional, Streichenberger, N, additional, Giraud, P, additional, Mousson-de-Camaret, B, additional, Montelescaut, M.E, additional, Broussolle, E, additional, and Chazot, G, additional
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- 2002
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109. Contributions of PET and SPECT to the understanding of the pathophysiology of Parkinson’s disease
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Thobois, S, primary, Guillouet, S, additional, and Broussolle, E, additional
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- 2001
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110. Severe dysphagia after botulinum toxin injection for cervical dystonia in multiple system atrophy
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Thobois, S., primary, Broussolle, E., additional, Toureille, L., additional, and Vial, C., additional
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- 2001
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111. Pre- and postnatal enzyme analysis for infantile,late infantile and adult neuronal ceroid lipofuscinosis (CLN 1 and CLN2)
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Van Diggelen, O.P., primary, Keulemans, J.L.M., additional, Kleijer, W.J., additional, Thobois, S., additional, Tilikete, C., additional, and Voznyi, Y.V., additional
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- 2001
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112. Motor imagery in normal subjects and in asymmetrical Parkinson's disease: A PET study
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Thobois, S., primary, Dominey, P. F., additional, Decety, J., additional, Pollak, P., additional, Gregoire, M. C., additional, Bars, D. L., additional, and Broussolle, E., additional
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- 2000
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113. Overactivation of primary motor cortex is asymmetrical in hemiparkinsonian patients
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Thobois, S, primary, Dominey, P, additional, Decety, J, additional, Pollak, P, additional, Gregoire, M C., additional, and Broussolle, E, additional
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- 2000
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114. Deep brain stimulation of the subthalamic nucleus, but not dopaminergic medication, improves proactive inhibitory control of movement initiation in Parkinson's disease.
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Favre E, Ballanger B, Thobois S, Broussolle E, Boulinguez P, Favre, Emilie, Ballanger, Bénédicte, Thobois, Stéphane, Broussolle, Emmanuel, and Boulinguez, Philippe
- Abstract
Slowness in movement initiation is a cardinal feature of Parkinson's disease (PD) that is still poorly understood and unsuccessfully alleviated by standard therapies. Here, we raise this major clinical issue within the framework of a novel theoretical model that allows a better understanding of the basic mechanisms involved in movement initiation. This model assumes that movement triggering is inhibited by default to prevent automatic responses to unpredictable events. We investigated to which extent the top-down control necessary to release this locking state before initiating actions is impaired in PD and restored by standard therapies. We used a cue-target reaction time task to test both the ability to initiate fast responses to targets and the ability to refrain from reacting to cues. Fourteen patients with dopaminergic (DA) medication and 11 with subthalamic nucleus (STN) stimulation were tested on and off treatment, and compared with 14 healthy controls. We found evidence that patients withdrawn from treatment have trouble voluntarily releasing proactive inhibitory control; while DA medication broadly reduces movement initiation latency, it does not reinstate a normal pattern of movement initiation; and stimulation of the STN specifically re-establishes the efficiency of the top-down control of proactive inhibition. These results suggest that movement initiation disorders that resist DA medication are due to executive, not motor, dysfunctions. This conclusion is discussed with regard to the role the STN may play as an interface between non-DA executive and DA motor systems in cortico-basal ganglia loops. [ABSTRACT FROM AUTHOR]
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- 2013
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115. Subthalamic stimulation in Parkinson's disease: restoring the balance of motivated behaviours.
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Lhommée E, Klinger H, Thobois S, Schmitt E, Ardouin C, Bichon A, Kistner A, Fraix V, Xie J, Aya Kombo M, Chabardès S, Seigneuret E, Benabid AL, Mertens P, Polo G, Carnicella S, Quesada JL, Bosson JL, Broussolle E, and Pollak P
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- 2012
116. Exhaustive analysis of BH4 and dopamine biosynthesis genes in patients with Dopa-responsive dystonia.
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Clot F, Grabli D, Cazeneuve C, Roze E, Castelnau P, Chabrol B, Landrieu P, Nguyen K, Ponsot G, Abada M, Doummar D, Damier P, Gil R, Thobois S, Ward AJ, Hutchinson M, Toutain A, Picard F, Camuzat A, and Fedirko E
- Abstract
Dopa-responsive dystonia is a childhood-onset dystonic disorder, characterized by a dramatic response to low dose of L-Dopa. Dopa-responsive dystonia is mostly caused by autosomal dominant mutations in the GCH1 gene (GTP cyclohydrolase1) and more rarely by autosomal recessive mutations in the TH (tyrosine hydroxylase) or SPR (sepiapterin reductase) genes. In addition, mutations in the PARK2 gene (parkin) which causes autosomal recessive juvenile parkinsonism may present as Dopa-responsive dystonia. In order to evaluate the relative frequency of the mutations in these genes, but also in the genes involved in the biosynthesis and recycling of BH4, and to evaluate the associated clinical spectrum, we have studied a large series of index patients (n = 64) with Dopa-responsive dystonia, in whom dystonia improved by at least 50% after L-Dopa treatment. Fifty seven of these patients were classified as pure Dopa-responsive dystonia and seven as Dopa-responsive dystonia-plus syndromes. All patients were screened for point mutations and large rearrangements in the GCH1 gene, followed by sequencing of the TH and SPR genes, then PTS (pyruvoyl tetrahydropterin synthase), PCBD (pterin-4a-carbinolamine dehydratase), QDPR (dihydropteridin reductase) and PARK2 (parkin) genes. We identified 34 different heterozygous point mutations in 40 patients, and six different large deletions in seven patients in the GCH1 gene. Except for one patient with mental retardation and a large deletion of 2.3 Mb encompassing 10 genes, all patients had stereotyped clinical features, characterized by pure Dopa-responsive dystonia with onset in the lower limbs and an excellent response to low doses of L-Dopa. Dystonia started in the first decade of life in 40 patients (85%) and before the age of 1 year in one patient (2.2%). Three of the 17 negative GCH1 patients had mutations in the TH gene, two in the SPR gene and one in the PARK2 gene. No mutations in the three genes involved in the biosynthesis and recycling of BH4 were identified. The clinical presentations of patients with mutations in TH and SPR genes were strikingly more complex, characterized by mental retardation, oculogyric crises and parkinsonism and they were all classified as Dopa-responsive dystonia-plus syndromes. Patient with mutation in the PARK2 gene had Dopa-responsive dystonia with a good improvement with L-Dopa, similar to Dopa-responsive dystonia secondary to GCH1 mutations. Although the yield of mutations exceeds 80% in pure Dopa-responsive dystonia and Dopa-responsive dystonia-plus syndromes groups, the genes involved are clearly different: GCH1 in the former and TH and SPR in the later. [ABSTRACT FROM AUTHOR]
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- 2009
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117. A multicentre study on suicide outcomes following subthalamic stimulation for Parkinson's disease.
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Voon V, Krack P, Lang AE, Lozano AM, Dujardin K, Schüpbach M, D'Ambrosia J, Thobois S, Tamma F, Herzog J, Speelman JD, Samanta J, Kubu C, Rossignol H, Poon Y, Saint-Cyr JA, Ardouin C, and Moro E
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- 2008
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118. Subthalamic nucleus stimulation and dysarthria in Parkinson's disease: a PET study.
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Pinto S, Thobois S, Costes N, Le Bars D, Benabid A, Broussolle E, Pollak P, and Gentil M
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- 2004
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119. Adult neuronal ceroid lipofuscinosis with palmitoyl-protein thioesterase deficiency: first adult-onset patients of a childhood disease.
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Van Diggelen, Otto P., Thobois, Stephane, Tilikete, Caroline, Zabot, Marie-Thérèse, Keulemans, Joke L. M., Van Bunderen, Patrick A., Taschner, Peter E. M., Losekoot, Monique, Voznyi, Yakov V., van Diggelen, O P, Thobois, S, Tilikete, C, Zabot, M T, Keulemans, J L, van Bunderen, P A, Taschner, P E, Losekoot, M, and Voznyi, Y V
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- 2001
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120. A rare case of SPG11mutation with multiple sclerosis
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Laurencin, C., Rascle, L., Cotton, F., Grosset-Janin, C., Bernard, E., Depienne, C., Vukusic, S., and Thobois, S.
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We describe a patient with SPG11hereditary spastic paraplegia (HSP), who developed walking disorder in childhood. He presented three episodes of subacute gait disorders worsening between the age of 20 and 22 years. Brain and spinal MRI revealed multiple T2 hypersignal lesions, consistent with inflammatory lesions. Surprisingly, CSF analysis showed neither oligoclonal bands nor increased IgG index. He was dramatically improved by intravenous methylprednisolone. A relapsing-remitting multiple sclerosis (MS) was suspected. This is the first description of SPG11HSP associated with MS.
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- 2016
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121. A multidisciplinary study of patients with early-onset PD with and without parkin mutationsSYMBOL
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Lohmann, E, Thobois, S, Lesage, S, Broussolle, E, Montcel, S Tezenas du, Ribeiro, M -J., Remy, P, Pelissolo, A, Dubois, B, Mallet, L, Pollak, P, Agid, Y, and Brice, A
- Abstract
To establish phenotype–genotype correlations in early-onset Parkinson disease (EOPD), we performed neurologic, neuropsychological, and psychiatric evaluations in a series of patients with and without parkin mutations.
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- 2009
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122. Myoclonus–dystonia
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Roze, E, Apartis, E, Clot, F, Dorison, N, Thobois, S, Guyant-Marechal, L, Tranchant, C, Damier, P, Doummar, D, Bahi-Buisson, N, André-Obadia, N, Maltete, D, Echaniz-Laguna, A, Pereon, Y, Beaugendre, Y, Dupont, S, De Greslan, T, Jedynak, C P., Ponsot, G, Dussaule, J C., Brice, A, Dürr, A, and Vidailhet, M
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To clarify the clinical and neurophysiologic spectrum of myoclonus–dystonia patients with mutations of the SGCEgene.
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- 2008
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123. Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (Melas) associated with a Fahr disease and cerebellar calcifications
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Younes-Mhenni, S., Thobois, S., Streichenberger, N., Giraud, P., Mousson-de-Camaret, B., Montelescaut, M.E., Broussolle, E., and Chazot, G.
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ACIDOSIS , *MITOCHONDRIAL pathology - Abstract
Introduction. – Melas syndrome is a mitochondrial disease which corresponds to the association of mitochondrial encephalopathy, lactic acidosis and stroke-like espisodes.Case report. – The authors report the case of a 39 year-old woman presenting with hearing loss, seizures, visual field deficit, three stroke-like episodes and calcifications of the basal ganglia and cerebellar dentate nuclei. Melas syndrome was suspected and confirmed by muscle biopsy, showing ragged red fibers and the presence of an A3243G mutation of mitochondrial DNA.Conclusion. – This clinical, pathological and radiological observation shows that intracerebral calcifications may involve the dentate nuclei of the cerebellum in the Melas syndrome. [Copyright &y& Elsevier]
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- 2002
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124. Falsely reassuring impedance in a patient with deep brain stimulation: a case report.
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Dib, A., Polo, G., Danaila, T., Laurencin, C., Prange, S., and Thobois, S.
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DEEP brain stimulation , *HYBRID systems , *PULSE generators , *GLOBUS pallidus , *GROWTH disorders , *REOPERATION - Abstract
This letter, published in the Journal of Neurology, discusses a case report of a patient with deep brain stimulation (DBS) who experienced a relapse of dystonia despite normal impedance measurements. The patient had a complete unilateral extension fracture, which was not detected by impedance testing. The delay in diagnosing the fracture could have had serious consequences for the patient. The authors emphasize the importance of radiological examination in cases of sudden deterioration in DBS patients, as normal impedance measurements do not rule out hardware malfunction. They also highlight the potential risks of performing an MRI in patients with broken leads or cables. [Extracted from the article]
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- 2024
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125. Screening for DJ-1mutations in early onset autosomal recessive parkinsonism
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Ibáñez, P., De Michele, G., Bonifati, V., Lohmann, E., Thobois, S., Pollak, P., Agid, Y., Heutink, P., Dürr, A., and Brice, A.
- Abstract
The DJ-1gene was identified as responsible for early onset autosomal recessive parkinsonism in two families (PARK7). In this study, after excluding mutations in the parkin gene, the authors screened a large series of early onset autosomal recessive parkinsonism families and consanguineous isolated patients of diverse geographic origins for DJ-1mutations. No mutations were found. This indicates that PARK7is not a common locus for early onset autosomal recessive parkinsonism, and that one or more new loci remains to be identified.
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- 2003
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126. A detailed clinical study of early-onset Parkinson patients
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Lohmann, E., Thobois, S., Laine, S., Tezenas, S., Broussolle, E., Pollak, P., Mallet, L., Dubois, B., Agid, Y., and Alexis Brice
127. A multitracer dopaminergic PET study of YOPD patients with and without parkin mutations
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Ribeiro, M. J., Thobois, S., Lohmann, Ebba, Du Montcel, Sophie Tezenas, Lesage, Suzanne, Pollak, Pierre, Broussolle, Emmanuel, Alexis Brice, and Remy, P.
128. On-line motor control in patients with Parkinson's disease
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Desmurget, M., Gaveau, V., Vindras, P., Turner, R. S., Broussolle, E., Thobois, S., Desmurget, M., Gaveau, V., Vindras, P., Turner, R. S., Broussolle, E., and Thobois, S.
- Abstract
Recent models based, in part on a study of Huntington's disease, suggest that the basal ganglia are involved in on-line movement guidance. Two experiments were conducted to investigate this idea. First, we studied advanced Parkinson's disease patients performing a reaching task known to depend on on-line guidance. The task was to ‘look and point' in the dark at visual targets displayed in the peripheral visual field. In some trials, the target location was slightly modified during saccadic gaze displacement (when vision is suppressed). In both patient and control groups, the target jump induced a gradual modification of the movement which diverged smoothly from its original path to reach the new target location. No deficit was found in the patients, except for an increased latency to respond to the target jump (Parkinson's disease: 243 ms; controls: 166 ms). A computational simulation indicated that this response slowing was likely to be a by-product of bradykinesia. The unexpected inconsistency between this result and previous reports was investigated in a second experiment. We hypothesized that the relevant factor was the characteristics of the corrections to be performed. To test this prediction, we investigated a task requiring corrections of the same type as investigated in Huntington's disease, namely large, consciously detected errors induced by large target jumps at hand movement onset. In contrast with the smooth adjustments observed in the first experiment, the subjects responded to the target jump by generating a discrete corrective sub-movement. While this iterative response was relatively rapid in the control subjects (220 ms), Parkinson's disease patients exhibited either dramatically late (>730 ms) or totally absent on-line corrections. When on-line corrections were absent, the initial motor response was completed before a second corrective response was initiated (the latency of the corrective response was the same as the latency of the initial respon
129. USP30: A new promising target for Parkinson's disease?
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Thobois, S.
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- 2015
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130. History of the 'geste antagoniste' sign in cervical dystonia.
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Poisson, A., Krack, P., Thobois, S., Loiraud, C., Serra, G., Vial, C., and Broussolle, E.
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CERVICAL vertebrae , *DYSTONIA , *GESTURE , *TORTICOLLIS , *HUMAN mechanics , *TWENTIETH century - Abstract
The geste antagoniste is a voluntary maneuver that temporarily reduces the severity of dystonic posture or movements. It is a classical feature of focal and particularly cervical dystonia. However, the precise historical aspects of geste antagoniste still remain obscure. The goals of this review were (1) to clarify the origin of the geste antagoniste sign; (2) to identify the factors that led to its diffusion in the international literature; (3) to follow the evolution of that term across the twentieth century. We used medical and neurological French, German and English literature of the late nineteenth and early twentieth centuries, and the PubMed database by entering the terms geste antagoniste, antagonistic gesture and sensory trick. The geste antagoniste sign is a legacy of the Paris Neurological School of the end of the nineteenth century. The term was introduced by Meige and Feindel in their 1902 book on tics, written in the vein of their master, Brissaud, who first described this sign in 1893. The almost immediate translations of this book by Giese into German and Kinnier Wilson into English contributed to the rapid spreading of the term geste antagoniste, which is still in use worldwide today. The term antagonistic gesture is the translation proposed by Kinnier Wilson, which also led to the use of the term geste antagonistique. The geste antagoniste sign has long been considered a solid argument for the psychogenic origins of dystonia until the 1980s when Marsden made strong arguments for its organic nature. [ABSTRACT FROM AUTHOR]
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- 2012
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131. Book Reviews.
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Carota, Antonio and Thobois, S.
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NONFICTION - Abstract
The article reviews the books including "Decision & Behavioral Choice Organized by Natural & Artificial Brains," by Kazuo Ishii, Kiyohisa Natsume and Akitoshi Hanazawa, part of the Brain-Inspired IT Series and "Deep Brain Stimulation for Parkinson's Disease," by Gordon H. Baltuch and Matthew B. Stern.
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- 2008
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132. Optimizing the deep brain stimulation care pathway in patients with Parkinson's disease.
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Thomas, N., Mertens, P., Danaila, T., Polo, G., Klinger, H., Broussolle, E., and Thobois, S.
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DEEP brain stimulation , *PARKINSON'S disease diagnosis , *PARKINSON'S disease patients , *TREATMENT of neurodegeneration - Abstract
Management of Parkinson's disease (PD) using deep brain stimulation (DBS) requires complex care in specialized, multidisciplinary centers. A well-organized, efficient patient flow is crucial to ensure that eligible patients can quickly access DBS. Delays or inefficiencies in patient care may impact a center's ability to meet demand, creating a capacity bottleneck. Analysis of the current practices within a center may help identify areas for improvement. After external audit of the DBS workflow of the Lyon Neurological Hospital and comparison with other European centers, manageable steps were suggested to restructure the care pathway. Propositions of the audit comprised, for example: (1) directly admitting referred patients to hospital, without a prior neurological outpatient visit and (2) including the preoperative anesthesia consultation in the hospital stay 1 month before surgery, not separately. This reorganization (between 2013 and 2016) was performed without increases in hospital medical resources or costs. The time from patients' first referral to surgery was reduced (from 22 to 16 months; p = 0.033), as was the number of pre- and postoperative patient visits (11-5; p = 0.025) and the total cumulative length of in-hospital stay (20.5-17.5 nights; p = 0.02). Ultimately, the total number of PD consultations increased (346-498 per year), as did the number of DBS implants per year (32-45 patients). In this single center experience, restructuring the DBS care pathway allowed a higher number of PD patients to benefit from DBS therapy, with a shorter waiting time and without decreasing the quality of care. [ABSTRACT FROM AUTHOR]
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- 2017
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133. Chapitre 11 - Imagerie cérébrale
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Thobois, S. and Broussolle, E.
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134. Neuroimaging biomarkers for clinical trials in atypical parkinsonian disorders: Proposal for a Neuroimaging Biomarker Utility System
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Thilo vanEimeren, Angelo Antonini, Daniela Berg, Nico Bohnen, Roberto Ceravolo, Alexander Drzezga, Günter U. Höglinger, Makoto Higuchi, Stephane Lehericy, Simon Lewis, Oury Monchi, Peter Nestor, Matej Ondrus, Nicola Pavese, María Cecilia Peralta, Paola Piccini, José Ángel Pineda‐Pardo, Irena Rektorová, María Rodríguez‐Oroz, Axel Rominger, Klaus Seppi, A. Jon Stoessl, Alessandro Tessitore, Stephane Thobois, Valtteri Kaasinen, Gregor Wenning, Hartwig R. Siebner, Antonio P. Strafella, James B. Rowe, MDS Neuroimaging Study Group and the JPND Working Group ASAP‐SynTau, van Eimeren, T., Antonini, A., Berg, D., Bohnen, N., Ceravolo, R., Drzezga, A., Hoglinger, G. U., Higuchi, M., Lehericy, S., Lewis, S., Monchi, O., Nestor, P., Ondrus, M., Pavese, N., Peralta, M. C., Piccini, P., Pineda-Pardo, J. A., Rektorova, I., Rodriguez-Oroz, M., Rominger, A., Seppi, K., Stoessl, A. J., Tessitore, A., Thobois, S., Kaasinen, V., Wenning, G., Siebner, H. R., Strafella, A. P., Rowe, J. B., Rowe, James [0000-0001-7216-8679], and Apollo - University of Cambridge Repository
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Future studies ,610 Medicine & health ,Neuroimaging ,Neuroimaging biomarkers ,Disease ,lcsh:Geriatrics ,lcsh:RC346-429 ,Special Section: Working Group Summaries for the European Joint Programme for Neurodegenerative Disease Research (JPND). (Guest Editors: Jorge Jovicich & Giovanni B. Frisoni) ,CBS ,03 medical and health sciences ,0302 clinical medicine ,MSA ,Medicine ,ddc:610 ,Neurodegeneration ,lcsh:Neurology. Diseases of the nervous system ,030304 developmental biology ,Trials ,PSP ,0303 health sciences ,business.industry ,Disease progression ,Biomarker ,3. Good health ,ddc ,Clinical trial ,lcsh:RC952-954.6 ,Psychiatry and Mental health ,PET ,Multicentric ,Multisite ,Harmonization ,Biomarker (medicine) ,CBD ,Neurology (clinical) ,Utility system ,business ,MRI ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Introduction Therapeutic strategies targeting protein aggregations are ready for clinical trials in atypical parkinsonian disorders. Therefore, there is an urgent need for neuroimaging biomarkers to help with the early detection of neurodegenerative processes, the early differentiation of the underlying pathology, and the objective assessment of disease progression. However, there currently is not yet a consensus in the field on how to describe utility of biomarkers for clinical trials in atypical parkinsonian disorders. Methods To promote standardized use of neuroimaging biomarkers for clinical trials, we aimed to develop a conceptual framework to characterize in more detail the kind of neuroimaging biomarkers needed in atypical parkinsonian disorders, identify the current challenges in ascribing utility of these biomarkers, and propose criteria for a system that may guide future studies. Results As a consensus outcome, we describe the main challenges in ascribing utility of neuroimaging biomarkers in atypical parkinsonian disorders, and we propose a conceptual framework that includes a graded system for the description of utility of a specific neuroimaging measure. We included separate categories for the ability to accurately identify an intention-to-treat patient population early in the disease (Early), to accurately detect a specific underlying pathology (Specific), and the ability to monitor disease progression (Progression). Discussion We suggest that the advancement of standardized neuroimaging in the field of atypical parkinsonian disorders will be furthered by a well-defined reference frame for the utility of biomarkers. The proposed utility system allows a detailed and graded description of the respective strengths of neuroimaging biomarkers in the currently most relevant areas of application in clinical trials., Highlights • Challenges in ascribing utility of neuroimaging biomarkers in clinical trials. • Criteria for utility of neuroimaging biomarkers in clinical trials. • Proposition of a formalized and graded utility description system.
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- 2018
135. Microstructure of the cerebellum and its afferent pathways underpins dystonia in myoclonus dystonia.
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Tarrano C, Zito G, Galléa C, Delorme C, McGovern EM, Atkinson-Clement C, Brochard V, Thobois S, Tranchant C, Grabli D, Degos B, Corvol JC, Pedespan JM, Krystkowiak P, Houeto JL, Degardin A, Defebvre L, Didier M, Valabrègue R, Apartis E, Vidailhet M, Roze E, and Worbe Y
- Abstract
Background and Purpose: Myoclonus dystonia due to a pathogenic variant in SGCE (MYC/DYT-SGCE) is a rare condition involving a motor phenotype associating myoclonus and dystonia. Dysfunction within the networks relying on the cortex, cerebellum, and basal ganglia was presumed to underpin the clinical manifestations. However, the microarchitectural abnormalities within these structures and related pathways are unknown. Here, we investigated the microarchitectural brain abnormalities related to the motor phenotype in MYC/DYT-SGCE., Methods: We used neurite orientation dispersion and density imaging, a multicompartment tissue model of diffusion neuroimaging, to compare microarchitectural neurite organization in MYC/DYT-SGCE patients and healthy volunteers (HVs). Neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISOVF) were derived and correlated with the severity of motor symptoms. Fractional anisotropy (FA) and mean diffusivity (MD) derived from the diffusion tensor approach were also analyzed. In addition, we studied the pathways that correlated with motor symptom severity using tractography analysis., Results: Eighteen MYC/DYT-SGCE patients and 24 HVs were analyzed. MYC/DYT-SGCE patients showed an increase of ODI and a decrease of FA within their motor cerebellum. More severe dystonia was associated with lower ODI and NDI and higher FA within motor cerebellar cortex, as well as with lower NDI and higher ISOVF and MD within the corticopontocerebellar and spinocerebellar pathways. No association was found between myoclonus severity and diffusion parameters., Conclusions: In MYC/DYT-SGCE, we found microstructural reorganization of the motor cerebellum. Structural change in the cerebellar afferent pathways that relay inputs from the spinal cord and the cerebral cortex were specifically associated with the severity of dystonia., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)
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- 2024
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136. Oxycodone or Higher Dose of Levodopa for the Treatment of Parkinsonian Central Pain: OXYDOPA Trial.
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Brefel-Courbon C, Harroch E, Marques A, Devos D, Thalamas C, Rousseau V, Ory-Magne F, Fabbri M, Maltête D, Rouaud T, Drapier S, Tir M, Thobois S, Salhi H, Corvol JC, Castelnovo G, Lagha-Boukbiza O, Fluchère F, Frismand S, Ansquer S, Sommet A, and Rascol O
- Abstract
Background: Among the different types of pain related to Parkinson's disease (PD), parkinsonian central pain (PCP) is the most disabling., Objectives: We investigated the analgesic efficacy of two therapeutic strategies (opioid with oxycodone- prolonged-release (PR) and higher dose of levodopa/benserazide) compared with placebo in patients with PCP., Methods: OXYDOPA was a randomized, double-blind, double-dummy, placebo-controlled, multicenter parallel-group trial run at 15 centers within the French NS-Park network. PD patients with PCP (≥30 on the Visual Analogue Scale [VAS]) were randomly assigned to receive oxycodone-PR (up to 40 mg/day), levodopa/benserazide (up to 200 mg/day) or matching placebo three times a day (tid) for 8 weeks at a stable dose, in add-on to their current dopaminergic therapy. The primary endpoint was the change in average pain intensity over the previous week rated on VAS from baseline to week-10 based on modified intention-to-treat analyses., Results: Between May 2016 and August 2020, 66 patients were randomized to oxycodone-PR (n = 23), levodopa/benserazide (n = 20) or placebo (n = 23). The mean change in pain intensity was -17 ± 18.5 on oxycodone-PR, -8.3 ± 11.1 on levodopa/benserazide, and -14.3 ± 18.9 in the placebo groups. The absolute difference versus placebo was -1.54 (97.5% confidence interval [CI], -17.0 to 13.90; P = 0.8) on oxycodone-PR and +7.79 (97.5% CI, -4.99 to 20.58; P = 0.2) on levodopa/benserazide. Similar proportions of patients in each group experienced all-cause adverse events. Those leading to study discontinuation were most frequently observed with oxycodone-PR (39%) than levodopa/benserazide (5%) or placebo (15%)., Conclusions: The present trial failed to demonstrate the superiority of oxycodone-PR or a higher dose of levodopa in patients with PCP, while oxycodone-PR was poorly tolerated. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)
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- 2024
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137. The impact of subthalamic deep-brain stimulation in restoring motor symmetry in Parkinson's disease patients: a prospective study.
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Barbosa RP, Moreau C, Rolland AS, Rascol O, Brefel-Courbon C, Ory-Magne F, Bastos P, de Barros A, Hainque E, Rouaud T, Marques A, Eusebio A, Benatru I, Drapier S, Guehl D, Maltete D, Tranchant C, Wirth T, Giordana C, Tir M, Thobois S, Hopes L, Hubsch C, Jarraya B, Corvol JC, Bereau M, Devos D, and Fabbri M
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- Humans, Male, Female, Middle Aged, Aged, Prospective Studies, Treatment Outcome, Functional Laterality physiology, Parkinson Disease therapy, Parkinson Disease physiopathology, Deep Brain Stimulation, Subthalamic Nucleus, Quality of Life, Activities of Daily Living
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Background and Objectives: The impact of subthalamic deep-brain stimulation (STN-DBS) on motor asymmetry and its influence on both motor and non-motor outcomes remain unclear. The present study aims at assessing the role of STN-DBS on motor asymmetry and how its modulation translates into benefits in motor function, activities of daily living (ADLs) and quality of life (QoL)., Methods: Postoperative motor asymmetry has been assessed on the multicentric, prospective Predictive Factors and Subthalamic Stimulation in Parkinson's Disease cohort. Asymmetry was evaluated at both baseline (pre-DBS) and 1 year after STN-DBS. A patient was considered asymmetric when the right-to-left MDS-UPDRS part III difference was ≥ 5. In parallel, analyses have been carried out using the absolute right-to-left difference. The proportion of asymmetric patients at baseline was compared to that in the post-surgery evaluation across different medication/stimulation conditions., Results: 537 PD patients have been included. The proportion of asymmetric patients was significantly reduced after both STN-DBS and medication administration (asymmetric patients: 50% in pre-DBS MedOFF, 35% in MedOFF/StimON, 26% in MedON/StimOFF, and 12% in MedON/StimON state). Older patients at surgery and with higher baseline UPDRS II scores were significantly less likely to benefit from STN-DBS at the level of motor asymmetry. No significant correlation between motor asymmetry and ADLs (UPDRS II) or overall QoL (PDQ-39) score was observed. Asymmetric patients had significantly higher mobility, communication, and daily living PDQ-39 sub-scores., Conclusions: Both STN-DBS and levodopa lead to a reduction in motor asymmetry. Motor symmetry is associated with improvements in certain QoL sub-scores., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)
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- 2024
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138. Guillain-Barré syndrome following subthalamic nucleus - Deep Brain Stimulation in Parkinson's disease: A case report.
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Theuriet J, Aguesse C, Bouhour F, Jomir L, Thobois S, and Prange S
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- Humans, Male, Middle Aged, Parkinson Disease therapy, Parkinson Disease complications, Deep Brain Stimulation adverse effects, Guillain-Barre Syndrome therapy, Guillain-Barre Syndrome etiology, Subthalamic Nucleus
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- 2024
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139. Noradrenergic alterations in Parkinson's disease: a combined 11C-yohimbine PET/neuromelanin MRI study.
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Laurencin C, Lancelot S, Brosse S, Mérida I, Redouté J, Greusard E, Lamberet L, Liotier V, Le Bars D, Costes N, Thobois S, Boulinguez P, and Ballanger B
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- Humans, Tremor complications, Carbon Radioisotopes metabolism, Positron-Emission Tomography, Norepinephrine metabolism, Locus Coeruleus metabolism, Magnetic Resonance Imaging, Parkinson Disease metabolism, Melanins
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Degeneration of the noradrenergic system is now considered a pathological hallmark of Parkinson's disease, but little is known about its consequences in terms of parkinsonian manifestations. Here, we evaluated two aspects of the noradrenergic system using multimodal in vivo imaging in patients with Parkinson's disease and healthy controls: the pigmented cell bodies of the locus coeruleus with neuromelanin sensitive MRI; and the density of α2-adrenergic receptors (ARs) with PET using 11C-yohimbine. Thirty patients with Parkinson's disease and 30 age- and sex-matched healthy control subjects were included. The characteristics of the patients' symptoms were assessed using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Patients showed reduced neuromelanin signal intensity in the locus coeruleus compared with controls and diminished 11C-yohimbine binding in widespread cortical regions, including the motor cortex, as well as in the insula, thalamus and putamen. Clinically, locus coeruleus neuronal loss was correlated with motor (bradykinesia, motor fluctuations, tremor) and non-motor (fatigue, apathy, constipation) symptoms. A reduction of α2-AR availability in the thalamus was associated with tremor, while a reduction in the putamen, the insula and the superior temporal gyrus was associated with anxiety. These results highlight a multifaceted alteration of the noradrenergic system in Parkinson's disease since locus coeruleus and α2-AR degeneration were found to be partly uncoupled. These findings raise important issues about noradrenergic dysfunction that may encourage the search for new drugs targeting this system, including α2-ARs, for the treatment of Parkinson's disease., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)
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- 2024
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140. Association of abnormal explicit sense of agency with cerebellar impairment in myoclonus-dystonia.
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Tarrano C, Galléa C, Delorme C, McGovern EM, Atkinson-Clement C, Barnham IJ, Brochard V, Thobois S, Tranchant C, Grabli D, Degos B, Corvol JC, Pedespan JM, Krystkowiak P, Houeto JL, Degardin A, Defebvre L, Valabrègue R, Beranger B, Apartis E, Vidailhet M, Roze E, and Worbe Y
- Abstract
Non-motor aspects in dystonia are now well recognized. The sense of agency, which refers to the experience of controlling one's own actions, has been scarcely studied in dystonia, even though its disturbances can contribute to movement disorders. Among various brain structures, the cerebral cortex, the cerebellum, and the basal ganglia are involved in shaping the sense of agency. In myoclonus dystonia, resulting from a dysfunction of the motor network, an altered sense of agency may contribute to the clinical phenotype of the condition. In this study, we compared the explicit and implicit sense of agency in patients with myoclonus dystonia caused by a pathogenic variant of SGCE (DYT- SGCE ) and control participants. We utilized behavioural tasks to assess the sense of agency and performed neuroimaging analyses, including structural, resting-state functional connectivity, and dynamic causal modelling, to explore the relevant brain regions involved in the sense of agency. Additionally, we examined the relationship between behavioural performance, symptom severity, and neuroimaging findings. We compared 19 patients with DYT- SGCE and 24 healthy volunteers. Our findings revealed that patients with myoclonus-dystonia exhibited a specific impairment in explicit sense of agency, particularly when implicit motor learning was involved. However, their implicit sense of agency remained intact. These patients also displayed grey-matter abnormalities in the motor cerebellum, as well as increased functional connectivity between the cerebellum and pre-supplementary motor area. Dynamic causal modelling analysis further identified reduced inhibitory effects of the cerebellum on the pre-supplementary motor area, decreased excitatory effects of the pre-supplementary motor area on the cerebellum, and increased self-inhibition within the pre-supplementary motor area. Importantly, both cerebellar grey-matter alterations and functional connectivity abnormalities between the cerebellum and pre-supplementary motor area were found to correlate with explicit sense of agency impairment. Increased self-inhibition within the pre-supplementary motor area was associated with less severe myoclonus symptoms. These findings highlight the disruption of higher-level cognitive processes in patients with myoclonus-dystonia, further expanding the spectrum of neurological and psychiatric dysfunction already identified in this disorder., Competing Interests: C.G., C.T., B.B., B.D., I.J.B., V.B., C.A.-C., L.D., P.K., J.-L.H., E.A., A.D., J.-M.P., M.V. and Y.W. have no disclosures relevant to this work. C.T. received a PhD grant from the ‘Fondation pour la Recherche Médicale’. C.D. has received a research grant from the Fédération Internationale de l'Automobile and travel funding from Merz Pharma, Abbvie, Boston Scientific and Medtronic. J.C.C. has served on advisory boards for Biogen, Denali, Idorsia, Prevail Therapeutic, Servier, Theranexus and UCB, and has received grants from Sanofi and the Michael J Fox Foundation for other projects. S.T. received grants from France Parkinson, PHRC and honorarium from Abbvie, Boston, Merz. E.M. has received speaking honoraria from AbbVie, Dutch MDS symposium, travel support from Elivie, served on an advisory board for AbbVie and received research grants from the STAR MD and the RCSI Richard Steeven’s Scholarship. D.G. has received grants from AP-HP (DRC-PHRC) and France Parkinson, served on scientific advisory boards for AbbVie and Zambon; received research funding from Air Liquide and Orkyn; received speech honoraria from Medtronic, Abbvie, Merz, Orkyn, Aguettant and EverPharma, and received travel funding from Abbvie and Merz. E.R. received honorarium for speech from Orkyn, Aguettant, Elivie and for participating in an advisory board from Merz-Pharma. He received research support from Merz-Pharma, Orkyn, Aguettant, Elivie, Ipsen, Everpharma, Fondation Desmarest, AMADYS, ADCY5.org, Fonds de dotation Patrick Brou de Laurière, Agence Nationale de la Recherche, Societé Française de Médecine Esthétique, Dystonia Medical Research Foundation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)
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- 2024
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141. Globus Pallidus Lesion With Iron Deposition and Dopaminergic Denervation in a Patient With a Pathogenic SLC6A1 Variant: A Case Report.
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Leclert V, Laurencin C, Ameli R, Hermier M, Flaus A, Prange S, Lesca G, and Thobois S
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Objectives: SLC6A1 -related disorders encompass heterogeneous neuropsychiatric manifestations through GABAergic dysregulation, without any specific abnormalities on brain MRI, nor evidence of dopaminergic cell loss on I
123 -FP-β-CIT SPECT. We report here a case of globus pallidus lesions and dopaminergic denervation in a patient with a pathogenic SLC6A1 variant., Methods: A 26-year-old female patient with intellectual disability, behavioral, and psychiatric disorders treated by neuroleptics for many years developed a parkinsonian syndrome associated with mild hand dystonia and chorea. A 3T brain MRI and I123 -FP-β-CIT SPECT were performed., Results: MRI of the brain found bilateral pallidal lesions consistent with neurodegeneration with iron accumulation. The I123 -FP-β-CIT SPECT showed bilateral striatal presynaptic dopaminergic denervation. Whole-genome sequencing revealed a pathogenic SLC6A1 de novo variant. No additional variant was found in any of the genes responsible for Neurodegeneration with Brain Iron Accumulation (NBIA)., Discussion: This is a description of dopaminergic denervation and globus pallidus lesions with iron accumulation related to a SLC6A1 pathogenic variant. These findings expand the phenotype of SLC6A1 -related disorder and suggest that it could be considered as a differential diagnosis of NBIA., Competing Interests: The authors report no relevant disclosures. Go to Neurology.org/NG for full disclosures., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)- Published
- 2024
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142. PSP-Richardson's Syndrome as a Rare Phenotypic Expression of Very Late-Onset Huntington's Disease: A Case Report.
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Prange S, Laurencin C, Roche P, Quadrio I, and Thobois S
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- Humans, Phenotype, Supranuclear Palsy, Progressive metabolism, Huntington Disease diagnosis
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- 2024
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143. Motivational and cognitive predictors of apathy after subthalamic nucleus stimulation in Parkinson's disease.
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Béreau M, Kibleur A, Servant M, Clément G, Dujardin K, Rolland AS, Wirth T, Lagha-Boukbiza O, Voirin J, Santin MDN, Hainque E, Grabli D, Comte A, Drapier S, Durif F, Marques A, Eusebio A, Azulay JP, Giordana C, Houeto JL, Jarraya B, Maltete D, Rascol O, Rouaud T, Tir M, Moreau C, Danaila T, Prange S, Tatu L, Tranchant C, Corvol JC, Devos D, Thobois S, Desmarets M, and Anheim M
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- Humans, Prospective Studies, Cognition, Treatment Outcome, Parkinson Disease complications, Subthalamic Nucleus physiology, Apathy physiology, Deep Brain Stimulation methods
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Postoperative apathy is a frequent symptom in Parkinson's disease patients who have undergone bilateral deep brain stimulation of the subthalamic nucleus. Two main hypotheses for postoperative apathy have been suggested: (i) dopaminergic withdrawal syndrome relative to postoperative dopaminergic drug tapering; and (ii) direct effect of chronic stimulation of the subthalamic nucleus. The primary objective of our study was to describe preoperative and 1-year postoperative apathy in Parkinson's disease patients who underwent chronic bilateral deep brain stimulation of the subthalamic nucleus. We also aimed to identify factors associated with 1-year postoperative apathy considering: (i) preoperative clinical phenotype; (ii) dopaminergic drug management; and (iii) volume of tissue activated within the subthalamic nucleus and the surrounding structures. We investigated a prospective clinical cohort of 367 patients before and 1 year after chronic bilateral deep brain stimulation of the subthalamic nucleus. We assessed apathy using the Lille Apathy Rating Scale and carried out a systematic evaluation of motor, cognitive and behavioural signs. We modelled the volume of tissue activated in 161 patients using the Lead-DBS toolbox and analysed overlaps within motor, cognitive and limbic parts of the subthalamic nucleus. Of the 367 patients, 94 (25.6%) exhibited 1-year postoperative apathy: 67 (18.2%) with 'de novo apathy' and 27 (7.4%) with 'sustained apathy'. We observed disappearance of preoperative apathy in 22 (6.0%) patients, who were classified as having 'reversed apathy'. Lastly, 251 (68.4%) patients had neither preoperative nor postoperative apathy and were classified as having 'no apathy'. We identified preoperative apathy score [odds ratio (OR) 1.16; 95% confidence interval (CI) 1.10, 1.22; P < 0.001], preoperative episodic memory free recall score (OR 0.93; 95% CI 0.88, 0.97; P = 0.003) and 1-year postoperative motor responsiveness (OR 0.98; 95% CI 0.96, 0.99; P = 0.009) as the main factors associated with postoperative apathy. We showed that neither dopaminergic dose reduction nor subthalamic stimulation were associated with postoperative apathy. Patients with 'sustained apathy' had poorer preoperative fronto-striatal cognitive status and a higher preoperative action initiation apathy subscore. In these patients, apathy score and cognitive status worsened postoperatively despite significantly lower reduction in dopamine agonists (P = 0.023), suggesting cognitive dopa-resistant apathy. Patients with 'reversed apathy' benefited from the psychostimulant effect of chronic stimulation of the limbic part of the left subthalamic nucleus (P = 0.043), suggesting motivational apathy. Our results highlight the need for careful preoperative assessment of motivational and cognitive components of apathy as well as executive functions in order to better prevent or manage postoperative apathy., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2024
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144. Clinical and genetic keys to cerebellar ataxia due to FGF14 GAA expansions.
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Méreaux JL, Davoine CS, Pellerin D, Coarelli G, Coutelier M, Ewenczyk C, Monin ML, Anheim M, Le Ber I, Thobois S, Gobert F, Guillot-Noël L, Forlani S, Jornea L, Heinzmann A, Sangare A, Gaymard B, Guyant-Maréchal L, Charles P, Marelli C, Honnorat J, Degos B, Tison F, Sangla S, Simonetta-Moreau M, Salachas F, Tchikviladzé M, Castelnovo G, Mochel F, Klebe S, Castrioto A, Fenu S, Méneret A, Bourdain F, Wandzel M, Roth V, Bonnet C, Riant F, Stevanin G, Noël S, Fauret-Amsellem AL, Bahlo M, Lockhart PJ, Brais B, Renaud M, Brice A, and Durr A
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- Child, Humans, Ataxia diagnosis, Ataxia genetics, Australia, Canada, Cross-Sectional Studies, Cerebellar Ataxia diagnosis, Cerebellar Ataxia genetics, Friedreich Ataxia genetics
- Abstract
Background: SCA27B caused by FGF14 intronic heterozygous GAA expansions with at least 250 repeats accounts for 10-60% of cases with unresolved cerebellar ataxia. We aimed to assess the size and frequency of FGF14 expanded alleles in individuals with cerebellar ataxia as compared with controls and to characterize genetic and clinical variability., Methods: We sized this repeat in 1876 individuals from France sampled for research purposes in this cross-sectional study: 845 index cases with cerebellar ataxia and 324 affected relatives, 475 controls, as well as 119 cases with spastic paraplegia, and 113 with familial essential tremor., Findings: A higher frequency of expanded allele carriers in index cases with ataxia was significant only above 300 GAA repeats (10.1%, n = 85) compared with controls (1.1%, n = 5) (p < 0.0001) whereas GAA
250-299 alleles were detected in 1.7% of both groups. Eight of 14 index cases with GAA250-299 repeats had other causal pathogenic variants (4/14) and/or discordance of co-segregation (5/14), arguing against GAA causality. We compared the clinical signs in 127 GAA≥300 carriers to cases with non-expanded GAA ataxia resulting in defining a key phenotype triad: onset after 45 years, downbeat nystagmus, episodic ataxic features including diplopia; and a frequent absence of dysarthria. All maternally transmitted alleles above 100 GAA were unstable with a median expansion of +18 repeats per generation (r2 = 0.44; p < 0.0001). In comparison, paternally transmitted alleles above 100 GAA mostly decreased in size (-15 GAA (r2 = 0.63; p < 0.0001)), resulting in the transmission bias observed in SCA27B pedigrees., Interpretation: SCA27B diagnosis must consider both the phenotype and GAA expansion size. In carriers of GAA250-299 repeats, the absence of documented familial transmission and a presentation deviating from the key SCA27B phenotype, should prompt the search for an alternative cause. Affected fathers have a reduced risk of having affected children, which has potential implications for genetic counseling., Funding: This work was supported by the Fondation pour la Recherche Médicale, grant number 13338 to JLM, the Association Connaître les Syndrome Cérébelleux - France (to GS) and by the European Union's Horizon 2020 research and innovation program under grant agreement No 779257 ("SOLVE-RD" to GS). DP holds a Fellowship award from the Canadian Institutes of Health Research (CIHR). SK received a grant (01GM1905C) from the Federal Ministry of Education and Research, Germany, through the TreatHSP network. This work was supported by the Australian Government National Health and Medical Research Council grants (GNT2001513 and MRFF2007677) to MB and PJL., Competing Interests: Declaration of interests MA received consulting fees from Reata pharmaceuticals, Merz, AbbVie, Orkyn, Ever Pharma, Ipsen; honoraria from Reata pharmaceuticals, Merz, AbbVie, Orkyn, Ever Pharma, Ipsen and participated on an advisory board for Reata Pharmaceuticals. ILB received grants from Pfizer, Fondation Plan Alzheimer, JPND/ANR, Alector; consulting fees from Prevail Therapeutics, Alector, JEITO and participated on an advisory board of Prevail Therapeutics. CM reveived financial support for attending meetings and travel from Nutricia and participated on an advisory board of Medesis Pharma society. BD had public funding contracts for Clinical Research: Contrat de Recherche Clinique (CRC) 2021 (APHP), CRC 2023 (APHP) and Agence Régionale de Santé (ARS); received honoraria from MERZ, IPSEN Pharma, LVL Medical; received support for attending meetings from MERZ Pharma, ADELIA; participated on an advisory board of MERZ, ORION Pharma and received equipment from MERZ. SF received support for participation in national and international meetings from Alnylam. MB received honoraria for thesis examinations; is member of Australian Academy of Health and Medical Sciences Australian Learned Academies Data Internetworking Network (ALADIN) Project Steering Committee; Australian Academy of Health and Medical Sciences Reports Committee; Clinical Genomics Advisory Committee, Kinghorn Sequencing Center; Gen V Scientific Advisory Committee, Murdoch Children's Research Institute; Viertel Foundation Medical Advisory Board; Australian Academy of Health and Medical Sciences Reports Committee; Present American Epilepsy Society Basic Sciences Committee; Gen V Bioresource Genetics Working Group. AD received grants from Biogen, WAVELIFE, ROCHE, TRIPLET Therapeutics, NIH RO1 (National Institute of Health), National Hospital Clinical Research Program; consulting fees from Wavelife science, ROCHE, TRIPLET Therapeutics, Pfizer, ASKBIO, Genome Quebec, VICO therapeutics; participated on an advisory board for REATA; is the president of the Société Francophone de Neurogénétique., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)- Published
- 2024
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145. A burning question from the first international BPAN symposium: is restoration of autophagy a promising therapeutic strategy for BPAN?
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Mollereau B, Hayflick SJ, Escalante R, Mauthe M, Papandreou A, Iuso A, Celle M, Aniorte S, Issa AR, Lasserre JP, Lesca G, Thobois S, Burger P, and Walter L
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- Animals, Humans, Autophagy genetics, Mutation, Neurons, Carrier Proteins genetics, Neurodegenerative Diseases genetics
- Abstract
Beta-propeller protein-associated neurodegeneration (BPAN) is a rare neurodegenerative disease associated with severe cognitive and motor deficits. BPAN pathophysiology and phenotypic spectrum are still emerging due to the fact that mutations in the WDR45 (WD repeat domain 45) gene, a regulator of macroautophagy/autophagy, were only identified a decade ago. In the first international symposium dedicated to BPAN, which was held in Lyon, France, a panel of international speakers, including several researchers from the autophagy community, presented their work on human patients, cellular and animal models, carrying WDR45 mutations and their homologs. Autophagy researchers found an opportunity to explore the defective function of autophagy mechanisms associated with WDR45 mutations, which underlie neuronal dysfunction and early death. Importantly, BPAN is one of the few human monogenic neurological diseases targeting a regulator of autophagy, which raises the possibility that it is a relevant model to directly assess the roles of autophagy in neurodegeneration and to develop autophagy restorative therapeutic strategies for more common disorders. Abbreviations: ATG: autophagy related; BPAN: beta-propeller protein-associated neurodegeneration; ER: endoplasmic reticulum; KO: knockout; NBIA: neurodegeneration with brain iron accumulation; PtdIns3P: phosphatidylinositol-3-phosphate; ULK1: unc-51 like autophagy activating kinase 1; WDR45: WD repeat domain 45; WIPI: WD repeat domain, phosphoinositide interacting.
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- 2023
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146. Imbalanced motivated behaviors according to motor sign asymmetry in drug-naïve Parkinson's disease.
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Béreau M, Castrioto A, Servant M, Lhommée E, Desmarets M, Bichon A, Pélissier P, Schmitt E, Klinger H, Longato N, Phillipps C, Wirth T, Fraix V, Benatru I, Durif F, Azulay JP, Moro E, Broussolle E, Thobois S, Tranchant C, Krack P, and Anheim M
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- Humans, Cross-Sectional Studies, Anxiety, Anxiety Disorders complications, Parkinson Disease complications, Apathy
- Abstract
Few studies have considered the influence of motor sign asymmetry on motivated behaviors in de novo drug-naïve Parkinson's disease (PD). We tested whether motor sign asymmetry could be associated with different motivated behavior patterns in de novo drug-naïve PD. We performed a cross-sectional study in 128 de novo drug-naïve PD patients and used the Ardouin Scale of Behavior in Parkinson's disease (ASBPD) to assess a set of motivated behaviors. We assessed motor asymmetry based on (i) side of motor onset and (ii) MDS-UPDRS motor score, then we compared right hemibody Parkinson's disease to left hemibody Parkinson's disease. According to the MDS-UPDRS motor score, patients with de novo right hemibody PD had significantly lower frequency of approach behaviors (p = 0.031), including nocturnal hyperactivity (p = 0.040), eating behavior (p = 0.040), creativity (p = 0.040), and excess of motivation (p = 0.017) than patients with de novo left hemibody PD. Patients with de novo left hemibody PD did not significantly differ from those with de novo right hemibody PD regarding avoidance behaviors including apathy, anxiety and depression. Our findings suggest that motor sign asymmetry may be associated with an imbalance between motivated behaviors in de novo drug-naïve Parkinson's disease., (© 2023. The Author(s).)
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- 2023
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147. Volumetric changes and clinical trajectories in Parkinson's disease: a prospective multicentric study.
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Marques A, Macias E, Pereira B, Durand E, Chassain C, Vidal T, Defebvre L, Carriere N, Fraix V, Moro E, Thobois S, Metereau E, Mangone G, Vidailhet M, Corvol JC, Lehéricy S, Menjot de Champfleur N, Geny C, Spampinato U, Meissner WG, Frismand S, Schmitt E, Doé de Maindreville A, Portefaix C, Remy P, Fénelon G, Houeto JL, Colin O, Rascol O, Peran P, Bonny JM, Fantini ML, and Durif F
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- Humans, Longitudinal Studies, Prospective Studies, Brain diagnostic imaging, Brain pathology, Atrophy pathology, Parkinson Disease complications
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Background: Longitudinal measures of structural brain changes using MRI in relation to clinical features and progression patterns in PD have been assessed in previous studies, but few were conducted in well-defined and large cohorts, including prospective clinical assessments of both motor and non-motor symptoms., Objective: We aimed to identify brain volumetric changes characterizing PD patients, and determine whether regional brain volumetric characteristics at baseline can predict motor, psycho-behavioral and cognitive evolution at one year in a prospective cohort of PD patients., Methods: In this multicentric 1 year longitudinal study, PD patients and healthy controls from the MPI-R2* cohort were assessed for demographical, clinical and brain volumetric characteristics. Distinct subgroups of PD patients according to motor, cognitive and psycho-behavioral evolution were identified at the end of follow-up., Results: One hundred and fifty PD patients and 73 control subjects were included in our analysis. Over one year, there was no significant difference in volume variations between PD and control subjects, regardless of the brain region considered. However, we observed a reduction in posterior cingulate cortex volume at baseline in PD patients with motor deterioration at one year (p = 0.017). We also observed a bilateral reduction of the volume of the amygdala (p = 0.015 and p = 0.041) and hippocampus (p = 0.015 and p = 0.053) at baseline in patients with psycho-behavioral deterioration, regardless of age, dopaminergic treatment and center., Conclusion: Brain volumetric characteristics at baseline may predict clinical trajectories at 1 year in PD as posterior cingulate cortex atrophy was associated with motor decline, while amygdala and hippocampus atrophy were associated with psycho-behavioral decline., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)
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- 2023
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148. Efficacy and safety of clonidine for the treatment of impulse control disorder in Parkinson's disease: a multicenter, parallel, randomised, double-blind, Phase 2b Clinical trial.
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Laurencin C, Timestit N, Marques A, Duchez DD, Giordana C, Meoni S, Huddlestone M, Danaila T, Anheim M, Klinger H, Vidal T, Fatisson M, Caire C, Nourredine M, Boulinguez P, Dhelens C, Ballanger B, Prange S, Bin S, and Thobois S
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- Humans, Clonidine adverse effects, Impulsive Behavior, Double-Blind Method, Treatment Outcome, Parkinson Disease complications, Parkinson Disease drug therapy, Parkinson Disease diagnosis, Disruptive, Impulse Control, and Conduct Disorders drug therapy, Disruptive, Impulse Control, and Conduct Disorders etiology
- Abstract
Background: Impulse control disorders (ICDs) are frequently encountered in Parkinson's disease (PD)., Objectives: We aimed to assess whether clonidine, an α2-adrenergic receptor agonist, would improve ICDs., Methods: We conducted a multicentre trial in five movement disorder departments. Patients with PD and ICDs (n = 41) were enrolled in an 8-week, randomised (1:1), double-blind, placebo-controlled study of clonidine (75 μg twice a day). Randomisation and allocation to the trial group were carried out by a central computer system. The primary outcome was the change at 8 weeks in symptom severity using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) score. A reduction of the most elevated subscore of the QUIP-RS of more than 3 points without any increase in the other QUIP-RS dimension defined success., Results: Between 15 May 2019 and 10 September 2021, 19 patients in the clonidine group and 20 patients in the placebo group were enrolled. The proportion difference of success in reducing QUIP-RS at 8 weeks, was 7% (one-sided upper 90% CI 27%) with 42.1% of success in the clonidine group and 35.0% in the placebo group. Compared to patients in the placebo group, patients in the clonidine group experienced a greater reduction in the total QUIP-RS score at 8 weeks (11.0 points vs. 3.6)., Discussion: Clonidine was well tolerated but our study was not enough powerful to demonstrate significant superiority compared to placebo in reducing ICDs despite a greater reduction of total QUIP score at 8 weeks. A phase 3 study should be conducted., Trial Registration: The study was registered (NCT03552068) on clinicaltrials.gov on June 11, 2018., (© 2023. The Author(s).)
- Published
- 2023
- Full Text
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149. Autosomal recessive pathogenic MSTO1 variants in hereditary optic atrophy.
- Author
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Gerber S, Lessard L, Rouzier C, Ait-El-Mkadem Saadi S, Ameli R, Thobois S, Abouaf L, Bouhour F, Kaplan J, Putoux A, Pegat A, and Rozet JM
- Subjects
- Humans, Cytoskeletal Proteins genetics, Mutation, Cell Cycle Proteins genetics, Optic Atrophies, Hereditary
- Abstract
Gerber et al report 2 autosomal recessive pathogenic Misato homolog 1 (MSTO1) variants causing hereditary optic atrophy and raise concerns about a previously identified dominant variant of MSTO1 by Gal et al (2017)., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)
- Published
- 2023
- Full Text
- View/download PDF
150. Semi-quantitative analysis of visually normal 123 I-FP-CIT across three large databases revealed no difference between control and patients.
- Author
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Flaus A, Philippe R, Thobois S, Janier M, and Scheiber C
- Abstract
Background: To show the equivalence between the specific binding ratios (SBR) of visually normal
123 I-FP-CIT SPECT scans from patients to those from healthy volunteers (Hv) or patients without dopaminergic degeneration to allow their use as a reference database., Methods: The SBR values of visually normal SPECT scans from 3 groups were studied: (1) suspected Parkinsonism and no diagnostic follow-up (ScanOnlyDB: n = 764, NM/CT 670 CZT, GE Healthcare), (2) no degenerative dopaminergic pathology after a 5-year follow-up (NoDG5YearsDB: n = 237, Symbia T2, Siemens Medical Solutions), and 3) Hv (HvDB: n = 118, commercial GE database). A general linear model (GLM) was constructed with caudate, putamen, and striatum SBR as the dependent variables, and age and gender as the independent variables. Following post-reconstruction harmonization of the data, DB were combined in pairs, ScanOnlyDB&NoDG5yearsDG and ScanOnlyDB&HvDB before performing GLM analysis. Additionally, ScanOnlyDB GLM estimates were compared to those published from Siemens commercial DB (SiemensDB) and ENC-DAT., Results: The dispersion parameters, R2 and the SBR coefficients of variation, did not differ between databases. For all volumes of interest and all databases, SBR decreased significantly with age (e.g., decrease per decade for the striatum: - 4.94% for ScanOnlyDB, - 4.65% for NoDG5YearsDB, - 5.69% for HvDB). There was a significant covariance between SBR and gender for ScanOnlyDB (P < 10-5 ) and NoDG5YearsDB (P < 10-2 ). The age-gender interaction was significant only for ScanOnlyDB (P < 10-2 ), and the p-value decreased to 10-6 after combining ScanOnlyDB with NoDG5YearsDB. ScanOnlyDB GLM estimates were not significantly different from those from SiemensDB or ENC-DAT except for age-gender interaction., Conclusion: SBR values distribution from visually normal scans were not different from the existing reference database, enabling this method to create a reference database by expert nuclear physicians. In addition, it showed a rarely described age-gender interaction related to its size. The proposed post-reconstruction harmonization method can also facilitate the use of semi-quantitative analysis., (© 2023. The Author(s).)- Published
- 2023
- Full Text
- View/download PDF
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