Publications by authors named "Bertrand Degos"

81 Publications

The Diagnostic Value of a Short Memory Test: The TNI-93.

J Alzheimers Dis 2021 Oct 19. Epub 2021 Oct 19.

Neurology Department, Avicenne hospital, APHP, Bobigny, Sorbonne Paris Nord, France.

Background: The TNI-93 is a quick memory test designed for all patients regardless of their education level. A significant proportion of patients with Alzheimer's disease (AD) are illiterate or poorly educated, and only a few memory tests are adapted for these patients.

Objective: In this study we aimed at assessing the diagnostic value of the TNI-93 for diagnosis of patients with biologically confirmed amyloid status.

Methods: We included all patients who had an analysis of AD cerebrospinal fluid biomarkers, a neuropsychological assessment including a TNI-93 and an anatomical brain imaging at Avicenne Hospital between January 2009 and November 2019. We compared the TNI-93 scores in patients with amyloid abnormalities (A+) and patients without amyloid abnormalities (A-) according to the AT(N) diagnostic criteria.

Results: 108 patients were included (mean age: 66.9±8.5 years old, mean education level: 8.9±5.2 years). Patients from the A + group (N= 80) were significantly more impaired than patients from the A- group (N= 28) on immediate recall (A+: 5.9±2.8; A-: 7.4±2.6; p = 0.001), free recall (A+: 3.5±2.7; A-: 5.9±2.8; p ≤ 0.001), total recall (A+: 5.7±3.5; A-:7.8±2.8; p ≤ 0.001), and on number of intrusions during the recall phase (A+: 1±1.8; A-: 0.1±0.3; p = 0.002). ROC curves revealed that the best scores to discriminate A + from A- patients were immediate recall (Area under curve (AUC): 0.70), number of encoding trials (AUC: 0.73), free recall (AUC: 0.74), and total recall (AUC: 0.74).

Conclusion: The TNI-93's immediate, free, and total recalls are valuable tools for the 39 diagnosis of AD.
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http://dx.doi.org/10.3233/JAD-210546DOI Listing
October 2021

Neurological consequences of recreational nitrous oxide abuse during SARS-CoV-2 pandemic.

J Neurol 2021 Aug 21. Epub 2021 Aug 21.

Service de Neurologie, APHP, Hôpital Avicenne, Hôpitaux Universitaires de Paris - Seine Saint Denis, Sorbonne Paris Nord, Bobigny, France.

Introduction: Recreational use of nitrous oxide (NO) is a growing practice in France and all around the world and is often associated with neurological complications. We report detailed clinical and paraclinical presentations of 12 patients with combined degeneration of the spinal cord and peripheral neuropathies in relation to NO consumption, possibly favored by lockdowns due to SARS-CoV-2 pandemic.

Results: With variable levels of consumption, the 12 patients presented spinal cord and/or peripheral nerve damage, with mostly motor and ataxic symptoms, motor axonal nerve damage, and medullary T2-weighted hyperintensities on MRI. There was a clear improvement in symptoms after vitamin B12 substitution, although some sequelae remained, particularly sensory.

Discussion: We report detailed clinical, electrophysiological, radiological, and biological consequences of NO abuse in 12 patients. Our data support the clinical and paraclinical observations reported in the literature. The mechanisms of neurological NO toxicity are still debated. There is currently no precise recommendation on the therapeutic management. The clinical evolution after vitamin B12 substitution seems sufficient but could depend on early management. Effective messages targeting at risk population, but also the health professionals involved, seem crucial as does a better legal framework for this growing practice.
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http://dx.doi.org/10.1007/s00415-021-10748-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379581PMC
August 2021

The wide spectrum of COVID-19 neuropsychiatric complications within a multidisciplinary centre.

Brain Commun 2021 17;3(3):fcab135. Epub 2021 Jun 17.

Service d'Addictologie, Assistance Publique Hôpitaux de Paris, Sorbonne Université, Pitié-Salpêtrière, Paris 75013, France.

A variety of neuropsychiatric complications has been described in association with COVID-19 infection. Large scale studies presenting a wider picture of these complications and their relative frequency are lacking. The objective of our study was to describe the spectrum of neurological and psychiatric complications in patients with COVID-19 seen in a multidisciplinary hospital centre over 6 months. We conducted a retrospective, observational study of all patients showing neurological or psychiatric symptoms in the context of COVID-19 seen in the medical and university neuroscience department of Assistance Publique Hopitaux de Paris-Sorbonne University. We collected demographic data, comorbidities, symptoms and severity of COVID-19 infection, neurological and psychiatric symptoms, neurological and psychiatric examination data and, when available, results from CSF analysis, MRI, EEG and EMG. A total of 249 COVID-19 patients with a neurological or psychiatric manifestation were included in the database and 245 were included in the final analyses. One-hundred fourteen patients (47%) were admitted to the intensive care unit and 10 (4%) died. The most frequent neuropsychiatric complications diagnosed were encephalopathy (43%), critical illness polyneuropathy and myopathy (26%), isolated psychiatric disturbance (18%) and cerebrovascular disorders (16%). No patients showed CSF evidence of SARS-CoV-2. Encephalopathy was associated with older age and higher risk of death. Critical illness neuromyopathy was associated with an extended stay in the intensive care unit. The majority of these neuropsychiatric complications could be imputed to critical illness, intensive care and systemic inflammation, which contrasts with the paucity of more direct SARS-CoV-2-related complications or post-infection disorders.
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http://dx.doi.org/10.1093/braincomms/fcab135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344449PMC
June 2021

A single-center series of 482 patients with functional motor disorders.

J Psychosom Res 2021 Sep 2;148:110565. Epub 2021 Jul 2.

Service de Neurologie, Hôpital Avicenne, Hôpitaux Universitaires de Paris - Seine Saint Denis, Sorbonne Paris Nord, AP-HP, Bobigny, France; Dynamics and Pathophysiology of Neuronal Networks Team, Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR7241/INSERM U1050, Université PSL, 75005 Paris, France.

Functional motor disorders (FMD) are common and disabling. They are known to predominantly affect women and young to middle-aged patients, although they also occur during childhood or in the elderly. Demographic and clinical characteristics of patients with FMD are poorly known, since large series of consecutive patients are scarce.

Methods: In a chart review study, we retrospectively abstracted data from consecutive FMD patients who were referred to the Neurophysiology Department of the Salpêtrière University Hospital between 2008 and 2016 for treatment with repeated transcranial magnetic stimulation.

Results: 482 patients were included. Most patients were women (73.7%). Median age at symptoms onset was 35.5 years and symptoms were mostly characterized by acute (47.3%) or subacute (46%) onset. Only 23% of patients were active workers, while 58.3% were unemployed because of FMD. Half of the patients had functional motor weakness (n = 241) whereas the other half had movement disorders (n = 241), mainly with tremor (21.1%) or dystonia (20.5%). Among all patients, 66.4% had psychiatric comorbidity and 82.6% reported a history of trauma in the 6 months before symptoms onset. No difference was found in age or gender according to clinical phenotypes.

Conclusion: This large series will contribute to better characterize FMDs.
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http://dx.doi.org/10.1016/j.jpsychores.2021.110565DOI Listing
September 2021

Long-term effect of apomorphine infusion in advanced Parkinson's disease: a real-life study.

NPJ Parkinsons Dis 2021 Jun 11;7(1):50. Epub 2021 Jun 11.

Neurology Department, Pitié-Salpêtrière Hospital, AP-HP, Paris, France.

Long-term effects of continuous subcutaneous apomorphine infusion (CSAI) on health-related quality of life (HRQoL) and predictors of CSAI discontinuation are poorly known. Data from consecutive advanced Parkinson's disease patients treated in routine care were retrospectively collected over 24 months after CSAI initiation, with a focus on the 39-item Parkinson's disease questionnaire (PDQ-39). We determined predictors of CSAI discontinuation and HRQoL improvement using multiple regression analysis. Of the 110 subjects evaluated over a 2-year period, 35% discontinued CSAI. Of those who continued treatment, HRQoL remained stable with a sustained reduction in motor fluctuations. The observed effect on dyskinesias was mild and transient. Of note, patients with preexisting impulse control disorders showed an overall good tolerability. PDQ-39 was the only baseline predictor of HRQoL improvement after 2 years of treatment. The presence of dyskinesias, poorer psychological status, shorter disease duration, male sex, and worse OFF state were predictors of discontinuation. Best candidates for CSAI are patients with: (i) poor baseline HRQoL and (ii) marked motor fluctuations.
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http://dx.doi.org/10.1038/s41531-021-00194-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196159PMC
June 2021

Thrombocytopenia and agranulocytosis in a FXTAS choreic patient treated with tetrabenazine.

Neurol Sci 2021 Aug 10;42(8):3475-3477. Epub 2021 May 10.

Service de Neurologie, APHP, Hôpital Avicenne, Hôpitaux Universitaires de Paris, Seine Saint Denis, Sorbonne Paris Nord, Bobigny, France.

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http://dx.doi.org/10.1007/s10072-021-05310-2DOI Listing
August 2021

Trans-Spinal Direct Current Stimulation for Managing Primary Orthostatic Tremor.

Mov Disord 2021 08 27;36(8):1835-1842. Epub 2021 Mar 27.

Institut du Cerveau / Paris Brain Institute, ICM, Hôpital de la Pitié-Salpêtrière, CNRS UMR 7225, Inserm U 1127, Sorbonne Université UM75, Paris, France.

Background: Primary orthostatic tremor (POT) is a rare disorder, characterized by 13 to 18 Hz tremor in the legs when standing and is often refractory to medical treatment. Epidural spinal cord stimulation has been proposed as an alternative treatment. However, this approach is invasive, which limits its application.

Objective: Trans-spinal direct current stimulation (tsDCS) is a non-invasive method to modulate spinal cord circuits. The aim of this proof-of-concept study was to investigate the potential beneficial effect of tsDCS in POT.

Methods: We conducted a double-blind, sham-controlled study in 16 patients with POT. In two separate visits, patients received sham tsDCS first followed by active (either cathodal or anodal) tsDCS. The primary outcome was the change in time in standing position. Secondary outcomes comprised quantitative assessment of tremor, measurement of corticospinal excitability including short-latency afferent inhibition, and clinical global impression-improvement (CGI-I). Measurements were made at baseline, after sham tsDCS, 0-30 min, and 30-60 min after active conditions.

Results: Cathodal-tsDCS reduced tremor amplitude and frequency and lowered corticospinal excitability whereas anodal-tsDCS reduced tremor frequency only. CGI-I scores positively correlated with the time in standing position after both active tsDCS conditions.

Conclusion: A single session of tsDCS can improve instability in POT. This opens a new vista for experimental treatment options using multiple sessions of spinal DC stimulation. © 2021 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28581DOI Listing
August 2021

Persistent bilateral Tapia syndrome following critical COVID-19.

Clin Neurophysiol 2021 02 29;132(2):505-506. Epub 2020 Dec 29.

Service de Neurologie, APHP, Hôpital Avicenne, Hôpitaux Universitaires de Paris - Seine Saint Denis, Sorbonne Paris Nord, Bobigny, France; Dynamics and Pathophysiology of Neuronal Networks Team, Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR7241/INSERM U1050, Université PSL, 75005 Paris, France. Electronic address:

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http://dx.doi.org/10.1016/j.clinph.2020.12.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771298PMC
February 2021

Automated Categorization of Parkinsonian Syndromes Using Magnetic Resonance Imaging in a Clinical Setting.

Mov Disord 2021 02 2;36(2):460-470. Epub 2020 Nov 2.

Paris Brain Institute-ICM, INSERM U 1127, CNRS UMR 7225, Sorbonne Université, UMR S 1127, CNRS UMR 7225, Paris, France.

Background: Machine learning algorithms using magnetic resonance imaging (MRI) data can accurately discriminate parkinsonian syndromes. Validation in patients recruited in routine clinical practice is missing.

Objective: The aim of this study was to assess the accuracy of a machine learning algorithm trained on a research cohort and tested on an independent clinical replication cohort for the categorization of parkinsonian syndromes.

Methods: Three hundred twenty-two subjects, including 94 healthy control subjects, 119 patients with Parkinson's disease (PD), 51 patients with progressive supranuclear palsy (PSP) with Richardson's syndrome, 35 with multiple system atrophy (MSA) of the parkinsonian variant (MSA-P), and 23 with MSA of the cerebellar variant (MSA-C), were recruited. They were divided into a training cohort (n = 179) scanned in a research environment and a replication cohort (n = 143) examined in clinical practice on different MRI systems. Volumes and diffusion tensor imaging (DTI) metrics in 13 brain regions were used as input for a supervised machine learning algorithm. To harmonize data across scanners and reduce scanner-dependent effects, we tested two types of normalizations using patient data or healthy control data.

Results: In the replication cohort, high accuracies were achieved using volumetry in the classification of PD-PSP, PD-MSA-C, PSP-MSA-C, and PD-atypical parkinsonism (balanced accuracies: 0.840-0.983, area under the receiver operating characteristic curves: 0.907-0.995). Performances were lower for the classification of PD-MSA-P, MSA-C-MSA-P (balanced accuracies: 0.765-0.784, area under the receiver operating characteristic curve: 0.839-0.871) and PD-PSP-MSA (balanced accuracies: 0.773). Performance using DTI was improved when normalizing by controls, but remained lower than that using volumetry alone or combined with DTI.

Conclusions: A machine learning approach based on volumetry enabled accurate classification of subjects with early-stage parkinsonism, examined on different MRI systems, as part of their clinical assessment. © 2020 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28348DOI Listing
February 2021

Prospective study on a fast-track training in psychiatry for medical students: the psychiatric hat game.

BMC Med Educ 2020 Oct 19;20(1):373. Epub 2020 Oct 19.

Neurology Unit, AP-HP, Avicenne University Hospital, Sorbonne Paris Nord, Bobigny, France.

Background: While medical students are losing interest in lectures in favor of other educational materials, many studies suggest the benefit of active learning, combined with gamified educational tools. The authors developed a psychiatric adaptation of the « Hat Game ». It was hypothesised that this game would increase both knowledge and motivation in medical students toward psychiatric semiology. The aim of the study was to assess the benefit of a Psychiatric Hat Game session for learning psychiatric symptoms in third-year medical students. Student performance was also evaluated at 3 months.

Methods: This gamified fast-track training consists of two teams and each team has to guess as many psychiatric semiology terms as possible using different techniques (i.e. speech, mime). The study involved a pre- and post-evaluation of knowledge (Multiple Choice Questions) and a satisfaction survey. Baseline, post-immediate, and three-months scores were compared by using Friedman analysis for paired samples. Comparisons of mean scores at two different times were performed by using Wilcoxon test for paired samples.

Results: One hundred and sixty-six students were proposed to take part in the study. Among them 129 completed the whole program (response rate = 77.7%). Mean scores measured at the three points in time were significantly different (p < 0.001, N = 129). Knowledge mean scores were significantly higher after the game than before (+ 28.6%, p < 0.001). Improvement was maintained 3 months after the game (+ 18.9%, p < 0.001). Satisfaction survey items highlighted that students enjoyed and would recommend this type of gamified training.

Conclusions: The Psychiatric Hat Game improved knowledge of psychiatric semiology in medical students. Results suggest that it is a promising and efficient tool to playfully teach medical semiology, with transferable features, utility and acceptability from one medical field to another. This study contributes to the growing body of knowledge advocating for serious games and gamified training in medical education.
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http://dx.doi.org/10.1186/s12909-020-02304-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574431PMC
October 2020

Genetic and Phenotypic Basis of Autosomal Dominant Parkinson's Disease in a Large Multi-Center Cohort.

Front Neurol 2020 28;11:682. Epub 2020 Jul 28.

Sorbonne Université, Unité Mixte de Recherche (UMR) 1127, Paris, France.

, and are unequivocally associated with autosomal dominant Parkinson's disease (PD). We evaluated the prevalence of , and mutations and associated clinical features in a large French multi-center cohort of PD patients. Demographic and clinical data were collected for 1,805 index cases (592 with autosomal dominant inheritance and 1,213 isolated cases) since 1990. All probands were screened with TaqMan assays for Gly2019Ser. In the absence of this mutation, the coding sequences of the three genes were analyzed by Sanger sequencing and/or next-generation sequencing. The data for the three genes were analyzed according to age at onset, family history, ethnic origin and clinical features. We identified 160 index cases (8.9%) with known pathogenic variants: 138 with pathogenic variants (7.6%), including 136 with the Gly2019Ser mutation, 19 with point mutations or genomic rearrangements (1.1%), and three with the Asp620Asn mutation (0.16%). Mutation frequencies were higher in familial than isolated cases, consistent with autosomal dominant inheritance (12.0 vs. 7.3%; OR 1.7, 95% CI [1.2-2.4], = 0.001). PD patients with variants were more likely to have higher rates of late-onset PD (>50 years; OR 1.5, 95% CI [1.0-2.1], = 0.03), whereas those with mutations tended to have earlier age at onset disease (≤ 50 years, = 0.06). The clinical features of carriers and those without any pathogenic variants in known PD-associated genes were similar. The likelihood of detecting disease-causing mutations was higher in cases compatible with autosomal dominant inheritance.
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http://dx.doi.org/10.3389/fneur.2020.00682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399219PMC
July 2020

Dissociation in reactive and proactive inhibitory control in Myoclonus dystonia.

Sci Rep 2020 08 18;10(1):13933. Epub 2020 Aug 18.

Sorbonne University, 75005, Paris, France.

Myoclonus-dystonia (MD) is a syndrome characterized by myoclonus of subcortical origin and dystonia, frequently associated with psychiatric comorbidities. The motor and psychiatric phenotypes of this syndrome likely result from cortico-striato-thamalo-cerebellar-cortical pathway dysfunction. We hypothesized that reactive and proactive inhibitory control may be altered in these patients. Using the Stop Signal Task, we assessed reactive and proactive inhibitory control in MD patients with (n = 12) and without (n = 21) deep brain stimulation of the globus pallidus interna and compared their performance to matched healthy controls (n = 24). Reactive inhibition was considered as the ability to stop an already initiated action and measured using the stop signal reaction time. Proactive inhibition was assessed through the influence of several consecutive GO or STOP trials on decreased response time or inhibitory process facilitation. The proactive inhibition was solely impaired in unoperated MD patients. Patients with deep brain stimulation showed impairment in reactive inhibition, independent of presence of obsessive-compulsive disorders. This impairment in reactive inhibitory control correlated with intrinsic severity of myoclonus (i.e. pre-operative score). The results point to a dissociation in reactive and proactive inhibitory control in MD patients with and without deep brain stimulation of the globus pallidus interna.
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http://dx.doi.org/10.1038/s41598-020-70926-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434767PMC
August 2020

The Role of Magnetic Resonance Imaging for the Diagnosis of Atypical Parkinsonism.

Front Neurol 2020 17;11:665. Epub 2020 Jul 17.

Institut du Cerveau et de la Moelle épinière-ICM, INSERM U 1127, CNRS UMR 7225, Sorbonne Université, UPMC Univ Paris 06, UMRS 1127, CNRS UMR 7225, Paris, France.

The diagnosis of Parkinson's disease and atypical Parkinsonism remains clinically difficult, especially at the early stage of the disease, since there is a significant overlap of symptoms. Multimodal MRI has significantly improved diagnostic accuracy and understanding of the pathophysiology of Parkinsonian disorders. Structural and quantitative MRI sequences provide biomarkers sensitive to different tissue properties that detect abnormalities specific to each disease and contribute to the diagnosis. Machine learning techniques using these MRI biomarkers can effectively differentiate atypical Parkinsonian syndromes. Such approaches could be implemented in a clinical environment and improve the management of Parkinsonian patients. This review presents different structural and quantitative MRI techniques, their contribution to the differential diagnosis of atypical Parkinsonian disorders and their interest for individual-level diagnosis.
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http://dx.doi.org/10.3389/fneur.2020.00665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380089PMC
July 2020

Isolated post SARS-CoV-2 diplopia.

J Neurol 2020 Nov 12;267(11):3128-3129. Epub 2020 Jun 12.

Service de Neurologie, APHP, Hôpital Avicenne, Hôpitaux Universitaires de Paris-Seine Saint Denis, Sorbonne Paris Nord, Bobigny, France.

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http://dx.doi.org/10.1007/s00415-020-09987-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292242PMC
November 2020

Post SARS-CoV-2 Guillain-Barré syndrome.

Clin Neurophysiol 2020 07 11;131(7):1652-1654. Epub 2020 May 11.

Service de Neurologie, APHP, Hôpital Avicenne, Hôpitaux Universitaires de Paris - Seine Saint Denis, Sorbonne Paris Nord, Bobigny, France; Dynamics and Pathophysiology of Neuronal Networks Team, Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR7241/INSERM U1050, MemoLife Labex, 75005 Paris, France. Electronic address:

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http://dx.doi.org/10.1016/j.clinph.2020.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212990PMC
July 2020

Deep brain stimulation-guided optogenetic rescue of parkinsonian symptoms.

Nat Commun 2020 05 13;11(1):2388. Epub 2020 May 13.

Dynamics and Pathophysiology of Neuronal Networks Team, Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR7241/INSERM U1050, MemoLife Labex, 75005, Paris, France.

Deep brain stimulation (DBS) of the subthalamic nucleus is a symptomatic treatment of Parkinson's disease but benefits only to a minority of patients due to stringent eligibility criteria. To investigate new targets for less invasive therapies, we aimed at elucidating key mechanisms supporting deep brain stimulation efficiency. Here, using in vivo electrophysiology, optogenetics, behavioral tasks and mathematical modeling, we found that subthalamic stimulation normalizes pathological hyperactivity of motor cortex pyramidal cells, while concurrently activating somatostatin and inhibiting parvalbumin interneurons. In vivo opto-activation of cortical somatostatin interneurons alleviates motor symptoms in a parkinsonian mouse model. A computational model highlights that a decrease in pyramidal neuron activity induced by DBS or by a stimulation of cortical somatostatin interneurons can restore information processing capabilities. Overall, these results demonstrate that activation of cortical somatostatin interneurons may constitute a less invasive alternative than subthalamic stimulation.
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http://dx.doi.org/10.1038/s41467-020-16046-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220902PMC
May 2020

Subcortical Myoclonus and Associated Dystonia in 22q11.2 Deletion Syndrome.

Tremor Other Hyperkinet Mov (N Y) 2019 24;10. Epub 2020 Jan 24.

Neurology Unit, Avicenne University Hospital, Hôpitaux Universitaires de Paris-Seine Saint Denis, Bobigny, FR.

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http://dx.doi.org/10.7916/tohm.v0.729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982424PMC
October 2021

[Movement disorders in the elderly].

Geriatr Psychol Neuropsychiatr Vieil 2019 12;17(4):395-404

Service de neurologie, Hôpital Avicenne, Hôpitaux Universitaires de Paris - Seine-Saint-Denis, Paris, Bobigny, France, Faculté de médecine, Université Paris 13, UFR SMBH 74, Bobigny, France, UMR CNRS 7241/Inserm U1050, Center for interdisciplinary research in biology (CIRB), Collège de France, Paris, France.

Movement disorders are frequent in the elderly, with various presentations and causes. We review the most frequent movement disorders encountered in the elderly. Their diagnosis, mainly based on clinical examination, is necessary due to their common occurrence and their impact on autonomy. Tremor is the most frequent movement disorder, including essential tremor and Parkinson's disease. Iatrogenic or metabolic causes should always be explored in case of any movement disorder. Many treatments can induce movement disorders, especially in the elderly, often heavily treated by medications in patients with impaired renal or/and hepatic function. Other causes of movement disorders that may be encountered in the elderly and their treatment are described. Treatment will be started according to the ratio between the benefit of the functional gain and iatrogenic risk in these frailed subjects.
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http://dx.doi.org/10.1684/pnv.2019.0825DOI Listing
December 2019

Multimodal Magnetic Resonance Imaging Quantification of Brain Changes in Progressive Supranuclear Palsy.

Mov Disord 2020 01 11;35(1):161-170. Epub 2019 Nov 11.

Institut du Cerveau et de la Moelle-ICM, Centre de NeuroImagerie de Recherche-CENIR, Paris, France.

Background: Progressive supranuclear palsy (PSP) is a neurodegenerative clinically heterogeneous disorder, formal diagnosis being based on postmortem histological brain examination.

Objective: We aimed to perform a precise in vivo staging of neurodegeneration in PSP using quantitative multimodal MRI. The ability of MRI biomarkers to differentiate PSP from PD was also evaluated.

Methods: Eleven PSP patients were compared to 26 age-matched healthy controls and 51 PD patients. Images were acquired at 3 Tesla (three-dimensional T -weighted, diffusion tensor, and neuromelanin-sensitive images) and 7 Tesla (three-dimensional-T * images). Regions of interest included the cortical areas, hippocampus, amygdala, basal ganglia, basal forebrain, brainstem nuclei, dentate nucleus, and cerebellum. Volumes, mean diffusivity, and fractional anisotropy were measured. In each region, a threshold value for group categorization was calculated, and four grades of change (0-3) were determined.

Results: PSP patients showed extensive volume decreases and diffusion changes in the midbrain, SN, STN, globus pallidus, basal forebrain, locus coeruleus, pedunculopontine nucleus, and dentate nucleus, in close agreement with the degrees of impairment in histological analyses. The predictive factors for the separation of PSP and healthy controls were, in descending order, the neuromelanin-based SN volume; midbrain fractional anisotropy; volumes of the midbrain, globus pallidus, and putamen; and fractional anisotropy in the locus coeruleus. The best predictors for separating PSP from PD were the neuromelanin-based volume in the SN, fractional anisotropy in the pons, volumes of the midbrain and globus pallidus, and fractional anisotropy in the basal forebrain.

Conclusions: These results suggest that it is possible to evaluate brain neurodegeneration in PSP noninvasively, even in small brainstem nuclei, in close agreement with previously published histological data. © 2019 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.27877DOI Listing
January 2020

Visual sensory processing is altered in myoclonus dystonia.

Mov Disord 2020 01 30;35(1):151-160. Epub 2019 Sep 30.

Sorbonne Université, Paris, France; Inserm U1127, CNRS UMR 7225, UM 75, ICM, Paris, France.

Background: Abnormal sensory processing, including temporal discrimination threshold, has been described in various dystonic syndromes.

Objective: To investigate visual sensory processing in DYT-SGCE and identify its structural correlates.

Methods: DYT-SGCE patients without DBS (DYT-SGCE-non-DBS) and with DBS (DYT-SGCE-DBS) were compared to healthy volunteers in three tasks: a temporal discrimination threshold, a movement orientation discrimination, and movement speed discrimination. Response times attributed to accumulation of sensory visual information were computationally modelized, with μ parameter indicating sensory mean growth rate. We also identified the structural correlates of behavioral performance for temporal discrimination threshold.

Results: Twenty-four DYT-SGCE-non-DBS, 13 DYT-SGCE-DBS, and 25 healthy volunteers were included in the study. In DYT-SGCE-DBS, the discrimination threshold was higher in the temporal discrimination threshold (P = 0.024), with no difference among the groups in other tasks. The sensory mean growth rate (μ) was lower in DYT-SGCE in all three tasks (P < 0.01), reflecting a slower rate of sensory accumulation for the visual information in these patients independent of DBS. Structural imaging analysis showed a thicker left primary visual cortex (P = 0.001) in DYT-SGCE-non-DBS compared to healthy volunteers, which also correlated with lower μ in temporal discrimination threshold (P = 0.029). In DYT-SGCE-non-DBS, myoclonus severity also correlated with a lower μ in the temporal discrimination threshold task (P = 0.048) and with thicker V1 on the left (P = 0.022).

Conclusion: In DYT-SGCE, we showed an alteration of the visual sensory processing in the temporal discrimination threshold that correlated with myoclonus severity and structural changes in the primary visual cortex. © 2019 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.27857DOI Listing
January 2020

Invalidation of Parkinson's disease diagnosis after years of follow-up based on clinical, radiological and neurophysiological examination.

J Neurol Sci 2019 Nov 9;406:116454. Epub 2019 Sep 9.

Service de Neurologie, Hôpital Avicenne, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris 13, 93000 Bobigny, France; Dynamics and Pathophysiology of Neuronal Networks Team, Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR7241/INSERM U1050, MemoLife Labex, 75005 Paris, France.

Introduction: Diagnosis of Parkinson's disease (PD) is mainly based on clinical features. Accurate neurological examination is required but dopamine transporter (DaT) single photon emission computed tomography (SPECT) could be perfomed to support the diagnosis in ambiguous cases. The aim of this work is to describe the characteristics of patients with a prolonged PD misdiagnosis.

Methods: We collected data from 24 patients initially diagnosed with PD who had an atypical long-term evolution. We analyzed demographic and clinical characteristics and antiparkinsonian drugs medication. Brain MRI, DaT-SPECT and/or accelerometry/electromyography (EMG) recording were performed in a subgroup of patients. We analyzed the causes of erroneous PD diagnosis as well as the final diagnoses.

Results: Mean age at PD diagnosis was 60.4 ± 14.8 years. Symptoms at onset were rest tremor (n = 19), gait instability (n = 7) and micrographia (n = 4). Mean duration before diagnosis correction was 8.4 ± 5.3 years. All patients were treated by antiparkinsonian drugs with a mean daily levodopa equivalent dose (LED) of 508.1 ± 528.4 mg. All 18 patients who underwent DaT-SPECT had a normal result. The most frequent final diagnoses were essential tremor (n = 11) and functional movement disorders (n = 9).

Conclusion: Cases that have been initially diagnosed as PD and then progress in an atypical long-duration fashion may have been misdiagnosed. Absence of genuine bradykinesia, non-sustained response to antiparkinsonian drugs, or absence of levodopa-related side effects should prompt the clinician to reappraise the diagnosis and to consider performing a DaT-SPECT.
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http://dx.doi.org/10.1016/j.jns.2019.116454DOI Listing
November 2019

Functional Motor Symptoms in Parkinson's Disease and Functional Parkinsonism: A Systematic Review.

J Neuropsychiatry Clin Neurosci 2020 30;32(1):4-13. Epub 2019 Aug 30.

Neurology Unit, Avicenne University Hospital, Hôpitaux Universitaires de Paris-Seine Saint Denis, Bobigny, France (Ambar Akkaoui, Degos, Garcin); Dynamics and Pathophysiology of Neuronal Networks Team, Center for Interdisciplinary Research in Biology, Collège de France, Paris (Degos); the Department of Psychiatry and Addictive Medicine, Assistance Publique-Hôpitaux de Paris (AP-HP), University Hospital Bichat-Claude Bernard, and Paris Diderot University, Paris (Geoffroy); the Department of Neurology, Salpêtrière Hospital, AP-HP, Paris (Roze); and Brain and Spine Institute, Faculty of Medicine of Sorbonne University, Paris (Roze, Garcin).

Objective: Whereas functional symptoms are common in Parkinson's disease (PD), a parkinsonian syndrome may occasionally reflect a pure functional disorder (also named functional parkinsonism [FP]). This review aimed to decipher these entities to clarify the link between functional manifestations and PD.

Methods: Following the PRISMA guidelines, the authors performed a systematic literature search of the PubMed and Science Direct databases for the period 1988 to December 2018 to identify studies of patients with either FP or PD associated with functional neurological symptoms.

Results: From the 844 articles screened, 22 were retained, including 12 studies of functional neurological symptoms in PD and 16 studies of FP. The studies of functional symptoms in PD included 121 patients-57% were women, and the mean age was 61.3 years. Psychiatric history (mostly depression) and exposure to triggering stressors were frequent: 60% and 82.5%, respectively. The most common symptom was tremor (33.8%), most often located on the side most affected by PD (50%). Studies of FP included a total of 120 patients-62% were women, and the mean age was 50.7 years. The first FP symptoms appeared on average 5 years before diagnosis, with an abrupt onset in half the cases; 67.6% had a psychiatric history, and 46.8% were exposed to triggering stressors, such as physical injury, stress at work, or loss of family or friends.

Conclusions: Findings suggest a possible relationship between PD and FP. Clinicians should keep in mind the possibility of functional symptoms in PD patients.
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http://dx.doi.org/10.1176/appi.neuropsych.19030058DOI Listing
October 2020

Are PSP patients included in clinical trials representative of the general PSP population?

Parkinsonism Relat Disord 2019 09 10;66:202-206. Epub 2019 Jul 10.

Sorbonne Université, Assistance Publique Hôpitaux de Paris, Institut du Cerveau et de la Moelle épinière, ICM, Inserm U 1127, CNRS UMR 7225, Department of Neurology, Hôpital Pitié-Salpêtrière, F-75013, Paris, France. Electronic address:

Background: Progressive supranuclear palsy (PSP) is a rare parkinsonian syndrome with a wide spectrum of clinical presentations. Recently, the MDS published revised diagnosis criteria to provide early and reliable diagnosis of PSP and its variants. Two large randomized clinical trials were initiated in 2017, but the question remains regarding the extrapolation of their results to the general PSP population.

Objective: To determine if PSP patients included in clinical trials are representative of the general PSP population.

Methods: We conducted a single center retrospective study of PSP patients referred to a tertiary department of Neurology (Pitié-Salpêtrière Hospital, Paris) for clinical diagnosis and clinical trial inclusion, over a 12-month period. We collected and analyzed gender, age at examination, age at disease onset, disease duration, and core clinical features regarding oculo-motor dysfunction, postural instability, akinesia and cognitive dysfunction, and inclusion/exclusion criteria of clinical trials to assess eligibility for inclusion. We assessed the relative proportions of different PSP subtypes, as defined by the MDS-PSP criteria, in the whole population compared to patients eligible in trials.

Results: 206 PSP patients were included, among which 175 (85%) were diagnosed with probable PSP-Richardson's syndrome (RS) subtype, with a mean age of 73 and mean disease duration of 5 years. Among those patients, 29 (21%) were eligible (age 71 ± 10.7, disease duration 3.1 ± 1.2 years) and 19 were included in trials, all with a diagnosis of probable PSP-RS. As compared to the whole population, patients included in clinical trials tended to be younger, and showed more PSP-RS subtypes (p < 0.05).

Conclusion: The PSP population included in trials is very similar to the general PSP population, but younger, with shorter disease duration. By definition, only probable PSP subtypes are included in clinical trials. The time window for inclusion is short because of diagnosis delay, fast disease progression and old age of the population.
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http://dx.doi.org/10.1016/j.parkreldis.2019.07.012DOI Listing
September 2019

Functional classification of ATM variants in ataxia-telangiectasia patients.

Hum Mutat 2019 10 17;40(10):1713-1730. Epub 2019 May 17.

CHU de Nancy, Service de Neurologie, Nancy, France.

Ataxia-telangiectasia (A-T) is a recessive disorder caused by biallelic pathogenic variants of ataxia-telangiectasia mutated (ATM). This disease is characterized by progressive ataxia, telangiectasia, immune deficiency, predisposition to malignancies, and radiosensitivity. However, hypomorphic variants may be discovered associated with very atypical phenotypes, raising the importance of evaluating their pathogenic effects. In this study, multiple functional analyses were performed on lymphoblastoid cell lines from 36 patients, comprising 49 ATM variants, 24 being of uncertain significance. Thirteen patients with atypical phenotype and presumably hypomorphic variants were of particular interest to test strength of functional analyses and to highlight discrepancies with typical patients. Western-blot combined with transcript analyses allowed the identification of one missing variant, confirmed suspected splice defects and revealed unsuspected minor transcripts. Subcellular localization analyses confirmed the low level and abnormal cytoplasmic localization of ATM for most A-T cell lines. Interestingly, atypical patients had lower kinase defect and less altered cell-cycle distribution after genotoxic stress than typical patients. In conclusion, this study demonstrated the pathogenic effects of the 49 variants, highlighted the strength of KAP1 phosphorylation test for pathogenicity assessment and allowed the establishment of the Ataxia-TeLangiectasia Atypical Score to predict atypical phenotype. Altogether, we propose strategies for ATM variant detection and classification.
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http://dx.doi.org/10.1002/humu.23778DOI Listing
October 2019

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

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

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

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

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

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

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

Conclusions: Our results report one of the biggest PD registries ever reported and demonstrate the feasibility of implementing a nation-wide registry of PD patients in France, a potent tool for future longitudinal studies and clinical trials' population selection, and for pharmaco-epidemiology and cost-effectiveness studies.
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http://dx.doi.org/10.1016/j.parkreldis.2019.04.012DOI Listing
July 2019

[Essential tremor].

Authors:
Bertrand Degos

Rev Prat 2018 Jun;68(6):654-656

Service de neurologie, hôpital Avicenne, Hôpitaux universitaires de Paris - Seine- Saint-Denis, AP-HP, Bobigny, France. Center for Interdisciplinary Research in Biology, Collège de France, Inserm U1050, CNRS UMR7241, Labex Memolife, Paris Sciences et Lettres, Paris, France.

Essential tremor. Essential tremor is very common in the general population. It is a postural tremor occurring in adulthood, evolving progressively and whose severity can be very variable from one individual to another. A positive effect of alcohol is often reported. Its pathophysiology remains poorly understood but candidate genes have been identified in some families. From a therapeutic point of view, a first-line treatment based on propanolol or primidone may be prescribed in case of discomfort. In case of inefficiency or intolerance, second-line treatments are available but their anti-tremor effect is very variable, depending on patients. In case of pharmacoresistance, the stimulation of the VIM nucleus of the thalamus is a very effective neurosurgical option. In the case of a contraindication to stimulation, gammaknife thalamotomy (radiosurgery) may also be considered. Recently, ultrasound thalamotomy has been shown to be a promising therapy in essential tremor.
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June 2018

Quality of life in functional movement disorders is as altered as in organic movement disorders.

J Psychosom Res 2019 01 12;116:10-16. Epub 2018 Nov 12.

Brain and Spine Institute, UPMC UMRS 1127, INSERM U1127, CNRS UMR 7225, Paris, France; Department of Neurology, Avicenne University Hospital, Paris - Seine Saint-Denis University Hospitals, Bobigny, France.

Objective: Patients with functional movement disorders (FMD) often report a disability and psychiatric comorbidities. However, few studies have compared these aspects in FMD and in organic movement disorders (OMD). The objectives were to compare QoL and psychiatric comorbidities of FMD and OMD patients.

Methods: Twenty-one and 30 FMD patients were compared to 21 and 30 sex- and age-matched dystonia and Parkinson patients respectively. QoL was assessed using the Parkinson's Disease Summary Index (PDSI). Psychiatric comorbidities were screened with the Mini International Neuropsychiatric Interview, the Hospital Anxiety and Depression Scale and the Composite International Diagnostic Interview questionnaire.

Results: QoL was more altered in FMD than in dystonia on PDSI (42.1 vs 25.1; p = .003). No significant difference was observed in QoL in FMD and Parkinson's disease on PDSI (38.3 vs 32.2; p = .61). Moreover, FMD patients were more often unemployed because of their condition than dystonia (61.9% vs 14.3%; p = .01) and Parkinson patients (53.3% vs 13.3%; p = .005). The occurrence of anxiety (p = .58 and > 0.99), depression (p = .77 and 0.77), and traumatic events (p = .58 and 0.75) was not different between groups. FMD patients reported more often sexual abuse than dystonia (28,6% vs 4.8%; p = .13) and Parkinson patients (23.3% vs 0.0%; p = .02).

Conclusion: FMD patients presented a significant alteration of QoL and no increased psychiatric comorbidities compared to OMD patients. These results highlight the impact of FMD and suggest that neurologists should be as involved in the management of FMD as they are in OMD.
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http://dx.doi.org/10.1016/j.jpsychores.2018.11.006DOI Listing
January 2019

The supplementary motor area modulates interhemispheric interactions during movement preparation.

Hum Brain Mapp 2019 05 17;40(7):2125-2142. Epub 2019 Jan 17.

Faculté de Médecine, INSERM U 1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière, Sorbonne Université, Paris, France.

The execution of coordinated hand movements requires complex interactions between premotor and primary motor areas in the two hemispheres. The supplementary motor area (SMA) is involved in movement preparation and bimanual coordination. How the SMA controls bimanual coordination remains unclear, although there is evidence suggesting that the SMA could modulate interhemispheric interactions. With a delayed-response task, we investigated interhemispheric interactions underlying normal movement preparation and the role of the SMA in these interactions during the delay period of unimanual or bimanual hand movements. We used functional MRI and transcranial magnetic stimulation in 22 healthy volunteers (HVs), and then in two models of SMA dysfunction: (a) in the same group of HVs after transient disruption of the right SMA proper by continuous transcranial magnetic theta-burst stimulation; (b) in a group of 22 patients with congenital mirror movements (CMM), whose inability to produce asymmetric hand movements is associated with SMA dysfunction. In HVs, interhemispheric connectivity during the delay period was modulated according to whether or not hand coordination was required for the forthcoming movement. In HVs following SMA disruption and in CMM patients, interhemispheric connectivity was modified during the delay period and the interhemispheric inhibition was decreased. Using two models of SMA dysfunction, we showed that the SMA modulates interhemispheric interactions during movement preparation. This unveils a new role for the SMA and highlights its importance in coordinated movement preparation.
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http://dx.doi.org/10.1002/hbm.24512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865634PMC
May 2019

Dopamine-endocannabinoid interactions mediate spike-timing-dependent potentiation in the striatum.

Nat Commun 2018 10 8;9(1):4118. Epub 2018 Oct 8.

Center for Interdisciplinary Research in Biology, College de France, INSERM U1050, CNRS UMR 7241, Labex Memolife, 75005, Paris, France.

Dopamine modulates striatal synaptic plasticity, a key substrate for action selection and procedural learning. Thus, characterizing the repertoire of activity-dependent plasticity in striatum and its dependence on dopamine is of crucial importance. We recently unraveled a striatal spike-timing-dependent long-term potentiation (tLTP) mediated by endocannabinoids (eCBs) and induced with few spikes (~5-15). Whether this eCB-tLTP interacts with the dopaminergic system remains to be investigated. Here, we report that eCB-tLTP is impaired in a rodent model of Parkinson's disease and rescued by L-DOPA. Dopamine controls eCB-tLTP via dopamine type-2 receptors (DR) located presynaptically in cortical terminals. Dopamine-endocannabinoid interactions via DR are required for the emergence of tLTP in response to few coincident pre- and post-synaptic spikes and control eCB-plasticity by modulating the long-term potentiation (LTP)/depression (LTD) thresholds. While usually considered as a depressing synaptic function, our results show that eCBs in the presence of dopamine constitute a versatile system underlying bidirectional plasticity implicated in basal ganglia pathophysiology.
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http://dx.doi.org/10.1038/s41467-018-06409-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175920PMC
October 2018
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