Publications by authors named "David Bendetowicz"

9 Publications

  • Page 1 of 1

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

Frontotemporal dementia subtypes based on behavioral inhibition deficits.

Alzheimers Dement (Amst) 2021 6;13(1):e12178. Epub 2021 Apr 6.

Paris Brain Institute Sorbonne Universités Paris France.

Introduction: We aimed to investigate phenotypic heterogeneity in the behavioral variant of frontotemporal dementia (bvFTD) through assessment of inhibition deficits.

Methods: We assessed occurrences of 16 behavioral inhibition deficits from video recordings of 15 bvFTD patients (early stage) and 15 healthy controls (HC) in an ecological setting. We extracted dimensions of inhibition deficit and analyzed their correlations with cognitive and clinical measures. Using these dimensions, we isolated patient clusters whose atrophy patterns were explored.

Results: After identifying two patterns of inhibition deficit (compulsive automatic behaviors and socially unconventional behaviors), we isolated three behavioral clusters with distinct atrophy patterns. BvFTD-G0 (N = 3), an outlier group, showed severe behavioral disturbances and more severe ventromedial prefrontal cortex/orbitofrontal cortex atrophy. Compared to bvFTD-G1 (N = 6), bvFTD-G2 (N = 6) presented higher anxiety and depression along with less diffuse atrophy especially in midline regions.

Discussion: Identifying clinico-anatomical profiles through behavior observation could help to stratify bvFTD patients for adapted treatments.
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http://dx.doi.org/10.1002/dad2.12178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022767PMC
April 2021

NeuroQ: A neurophobia screening tool assesses how roleplay challenges neurophobia.

J Neurol Sci 2021 Feb 20;421:117320. Epub 2021 Jan 20.

AP-HP, Hôpital Pitié-Salpêtrière, Département de Neurologie, Paris, France; Sorbonne Université, France; INSERM U1127, CNRS 7225, Institut du Cerveau, Paris, France.

Background: Neurophobia is a chronic disease of medical students and junior doctors. Early detection is needed to facilitate prevention and management as this fear can negatively impact patient care.

Methods: We conducted a two-part mono-centric study at the faculty of Medicine, Sorbonne University, in Paris. Part one: a cross-sectional study to validate a newly constructed neurophobia scale, NeuroQ. Part two: a prospective longitudinal study to assess the impact of The Move on student neurophobia using NeuroQ. A population-based sample of second-year medical students of the 2019 and 2020 class of the Faculty of Medicine of Sorbonne University were invited to participate.

Results: NeuroQ incorporates the main themes of the neurophobia definition and demonstrates uni-dimensionality. Three hundred and ninety-five medical students participated in the study (mean age was 20.0 years, SD: 2.1 years) assessing the effect of The Move teaching on neurophobia. Two hundred and eighty-eight (72.9%) students were female. After the Move teaching the mean NeuroQ score was significantly lower compared to the baseline NeuroQ score (mean [SD] variation, -1.1 [2.6], p < 0.001). There was a 22.3% relative reduction in the number of neurophobic students after The Move teaching.

Conclusion: Our results highlight the utility of NeuroQ in assessing (i) baseline neurophobia and (ii) the impact of pre-clinical educational interventions on neurophobia. Furthermore, we have shown the importance of pre-clinical educational interventions, such as The Move, in tackling neurophobia.
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http://dx.doi.org/10.1016/j.jns.2021.117320DOI Listing
February 2021

Current challenges in the pathophysiology, diagnosis, and treatment of paroxysmal movement disorders.

Expert Rev Neurother 2021 Jan 8;21(1):81-97. Epub 2020 Nov 8.

Département de Neurologie, AP-HP, Hôpital Pitié-Salpêtrière , Paris, France.

Introduction: Paroxysmal movement disorders mostly comprise paroxysmal dyskinesia and episodic ataxia, and can be the consequence of a genetic disorder or symptomatic of an acquired disease.

Areas Covered: In this review, the authors focused on certain hot-topic issues in the field: the respective contribution of the cerebellum and striatum to the generation of paroxysmal dyskinesia, the importance of striatal cAMP turnover in the pathogenesis of paroxysmal dyskinesia, the treatable causes of paroxysmal movement disorders not to be missed, with a special emphasis on the treatment strategy to bypass the glucose transport defect in paroxysmal movement disorders due to GLUT1 deficiency, and functional paroxysmal movement disorders.

Expert Opinion: Treatment of genetic causes of paroxysmal movement disorders is evolving towards precision medicine with targeted gene-specific therapy. Alteration of the cerebellar output and modulation of the striatal cAMP turnover offer new perspectives for experimental therapeutics, at least for paroxysmal movement disorders due to selected causes. Further characterization of cell-specific molecular pathways or network dysfunctions that are critically involved in the pathogenesis of paroxysmal movement disorders will likely result in the identification of new biomarkers and testing of innovative-targeted therapeutics.
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http://dx.doi.org/10.1080/14737175.2021.1840978DOI Listing
January 2021

Exploration Deficits Under Ecological Conditions as a Marker of Apathy in Frontotemporal Dementia.

Front Neurol 2019 28;10:941. Epub 2019 Aug 28.

Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06, Institut du Cerveau et de la Moelle épiniére (ICM), FRONTlab, Paris, France.

Apathy is one of the six clinical criteria for the behavioral variant of frontotemporal dementia (bvFTD), and it is almost universal in this disease. Although its consequences in everyday life are debilitating, its underlying mechanisms are poorly known, its assessment is biased by subjectivity and its care management is very limited. In this context, we have developed "," a method aimed at providing quantifiable and objective signature(s) of apathy in order to assess it and identify its precise underlying mechanisms. consists of the observation and recording of the patient's behavior when the participant is being submitted to a multiple-phase scenario reproducing a brief real-life situation. It is performed in a functional exploration platform transformed into a fully furnished waiting room equipped with a video and sensor-based data acquisition system. This multimodal method allowed video-based behavior analyses according to predefined behavioral categories (exploration behavior, sustained activities or inactivity) and actigraphy analyses from a 3D accelerometer. The data obtained were also correlated with behavioral/cognitive tests and scales assessing global cognitive efficiency, apathy, cognitive disinhibition, frontal syndrome, depression and anxiety. Here, bvFTD patients ( = 14) were compared to healthy participants ( = 14) during the very first minutes of the scenario, when the participants discovered the room and were encouraged to explore it. We showed that, in the context of facing a new environment, healthy participants first explored it and then engaged in sustained activities. By contrast, bvFTD patients were mostly inactive and eventually explored this new place, but in a more irregular and less efficient mode than normal subjects. This exploration deficit was correlated with apathy, disinhibition and cognitive and behavioral dysexecutive syndromes. These findings led us to discuss the presumed underlying mechanisms responsible for the exploration deficit (an inability to self-initiate actions, to integrate reward valuation and to inhibit involuntary behavior). Altogether, these results pave the way for simple and objective assessment of behavioral changes that represents a critical step for the evaluation of disease progression and efficacy of treatment in bvFTD.
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http://dx.doi.org/10.3389/fneur.2019.00941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736613PMC
August 2019

Two critical brain networks for generation and combination of remote associations.

Brain 2018 01;141(1):217-233

Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, Institut du cerveau et la moelle épinière (ICM) - FrontLab, Hôpital Pitié-Salpêtrière, Boulevard de l'hôpital, F-75013, Paris, France.

Recent functional imaging findings in humans indicate that creativity relies on spontaneous and controlled processes, possibly supported by the default mode and the fronto-parietal control networks, respectively. Here, we examined the ability to generate and combine remote semantic associations, in relation to creative abilities, in patients with focal frontal lesions. Voxel-based lesion-deficit mapping, disconnection-deficit mapping and network-based lesion-deficit approaches revealed critical prefrontal nodes and connections for distinct mechanisms related to creative cognition. Damage to the right medial prefrontal region, or its potential disrupting effect on the default mode network, affected the ability to generate remote ideas, likely by altering the organization of semantic associations. Damage to the left rostrolateral prefrontal region and its connections, or its potential disrupting effect on the left fronto-parietal control network, spared the ability to generate remote ideas but impaired the ability to appropriately combine remote ideas. Hence, the current findings suggest that damage to specific nodes within the default mode and fronto-parietal control networks led to a critical loss of verbal creative abilities by altering distinct cognitive mechanisms.
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http://dx.doi.org/10.1093/brain/awx294DOI Listing
January 2018

Brain morphometry predicts individual creative potential and the ability to combine remote ideas.

Cortex 2017 01 15;86:216-229. Epub 2016 Nov 15.

Inserm, U 1127, Paris, France; CNRS, UMR 7225, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Paris, France; ICM, FrontLab, Hôpital Pitié Salpêtrière, Paris; ICM, CENIR, Paris, France. Electronic address:

For complex mental functions such as creative thinking, inter-individual variability is useful to better understand the underlying cognitive components and brain anatomy. Associative theories propose that creative individuals have flexible semantic associations, which allows remote elements to be formed into new combinations. However, the structural brain variability associated with the ability to combine remote associates has not been explored. To address this question, we performed a voxel-based morphometry (VBM) study and explored the anatomical connectivity of significant regions. We developed a Remote Combination Association Task adapted from Mednick's test, in which subjects had to find a solution word related to three cue words presented to them. In our adaptation of the task, we used free association norms to quantify the associative distance between the cue words and solution words, and we varied this distance. The tendency to solve the task with insight and the ability to evaluate the appropriateness of a proposed solution were also analysed. Fifty-four healthy volunteers performed this task and underwent a structural MRI. Structure-function relationships were analysed using regression models between grey matter (GM) volume and task performance. Significant clusters were mapped onto an atlas of white matter (WM) tracts. The ability to solve the task, which depended on the associative distance of the solution word, was associated with structural variation in the left rostrolateral prefrontal and posterior parietal regions; the left rostral prefrontal region was connected to distant regions through long-range pathways. By using a creative combination task in which the semantic distance between words varied, we revealed a brain network centred on the left frontal pole that appears to support the ability to combine information in new ways by bridging the semantic distance between pieces of information.
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http://dx.doi.org/10.1016/j.cortex.2016.10.021DOI Listing
January 2017

Reasoning by analogy requires the left frontal pole: lesion-deficit mapping and clinical implications.

Brain 2016 06 13;139(Pt 6):1783-99. Epub 2016 Apr 13.

1 Inserm, U 1127, 75013 Paris, France 2 CNRS, UMR 7225, 75013 Paris, France 3 Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, 75013 Paris, France 4 ICM, FrontLab, 75013 Paris, France 6 ICM, Brain Connectivity and Behaviour, 75013 Paris, France 13 CENIR, ICM, 75013 Paris, France

SEE BURGESS DOI101093/BRAIN/AWW092 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE  : Analogical reasoning is at the core of the generalization and abstraction processes that enable concept formation and creativity. The impact of neurological diseases on analogical reasoning is poorly known, despite its importance in everyday life and in society. Neuroimaging studies of healthy subjects and the few studies that have been performed on patients have highlighted the importance of the prefrontal cortex in analogical reasoning. However, the critical cerebral bases for analogical reasoning deficits remain elusive. In the current study, we examined analogical reasoning abilities in 27 patients with focal damage in the frontal lobes and performed voxel-based lesion-behaviour mapping and tractography analyses to investigate the structures critical for analogical reasoning. The findings revealed that damage to the left rostrolateral prefrontal region (or some of its long-range connections) specifically impaired the ability to reason by analogies. A short version of the analogy task predicted the existence of a left rostrolateral prefrontal lesion with good accuracy. Experimental manipulations of the analogy tasks suggested that this region plays a role in relational matching or integration. The current lesion approach demonstrated that the left rostrolateral prefrontal region is a critical node in the analogy network. Our results also suggested that analogy tasks should be translated to clinical practice to refine the neuropsychological assessment of patients with frontal lobe lesions.
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http://dx.doi.org/10.1093/brain/aww072DOI Listing
June 2016

Diagnostic Yield of Venous Thrombosis and Pulmonary Embolism by Combined CT Venography and Pulmonary Angiography in Patients with Cryptogenic Stroke and Patent Foramen Ovale.

Eur Neurol 2015 25;74(1-2):69-72. Epub 2015 Jul 25.

Division of Neurology, Stroke Center, Foch Hospital, University Versailles Saint-Quentin en Yvelines, Suresnes, France.

Background: Paradoxical embolism via a patent foramen ovale (PFO) has been suggested as a potential stroke mechanism. Combined CT venography and pulmonary angiography (CVPA) is a simple, validated and accurate technique to diagnose deep venous thrombosis (DVT) or pulmonary embolism (PE). We sought to assess the prevalence of DVT or PE among patients with PFO and cryptogenic stroke (CS) by CVPA.

Methods: Patients were identified retrospectively from a clinical registry of consecutive patients with stroke admitted to our Stroke Unit. The following criteria were required for inclusion in this study: CS, PFO identified by transthoracic echography using contrast medium and CVPA performed during the hospitalization following stroke.

Results: A total of 114 patients with PFO underwent a CVPA within 7 days (interquartile range 4-9) from stroke symptom onset. On cerebral imaging, 11% had multiple infarcts. CVPA documented deep vein thrombosis (DVT) in 10 patients (8.8%) and PE in 5 patients (4.4%), that is, a total of 12 patients with prevalence of 10.5% (95% CI 5.5-17.7). Patients with PE-DVT had higher D-dimers and C reactive protein level than patients without PE-DVT (p < 0.05).

Conclusion: CVPA may be used by the stroke team in the work-up of suspected paradoxical embolism among cryptogenic ischemic stroke patients with PFO.
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http://dx.doi.org/10.1159/000437261DOI Listing
June 2016
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