Arnaud Delval | Université de Lille (original) (raw)

Papers by Arnaud Delval

Revue Neurologique, 2004

Les neuropathies périphériques associées à une gammapathie monoclonale de type IgM sont d’individ... more Les neuropathies périphériques associées à une gammapathie monoclonale de type IgM sont d’individualisation récente. Des autoanticorps sont susceptibles de réagir avec les glycoprotéines constitutives du nerf que ce soit la MAG (myelin associated protein) ou d’autres gangliosides contenant un acide sialique tels que le GM1, ou plusieurs acides sialiques tels que le GD3, le GD1b, le GT1b, le GQ1b.Nous décrivons trois cas de patients présentant des troubles oculomoteurs, une neuropathie sensitive ataxiante chronique, une vitesse de sédimentation élevée, une gammapathie monoclonale de type IgM, des anticorps anti-gangliosides disialylés, et la présence d’agglutinines froides réalisant un syndrome de type « CANOMAD » pour « chronic ataxic neuropathy with ophtalmoplegia, M protein, agglutination and disialosyl antibodies ».Un des cas était associé à une glomérulopathie de type extramembraneuse et à une atteinte motrice sévère. La physiopathologie de cette glomérulopathie apparaît liée à la polyneuropathie. La réponse des patients aux différents traitements (corticothérapie, immunoglobulines polyvalentes, cyclophosphamide) ne permet pas d’établir de consensus thérapeutique à ce jour.Cette étude montre que le spectre de ces neuropathies associées à une dysglobulinémie apparaît plus large que celui décrit initialement.Polyneuropathies associated with IgM monoclonal gammopathy were recently recognized. Antibodies can react with glycoproteins such as myelin associated glycoprotein (MAG), or gangliosides containing one sialosyl epitope such as GM1 or several sialosyl epitopes (polysialyted gangliosides) including GD2, GD3, GT1b, GT1a, GQ1b.We report on three patients presenting oculomotor dysfunction, chronic sensitive ataxic polyneuropathy, high sedimentation rate, IgM monoclonal paraprotein of unknown signification and antidisialosyl IgM antibodies and for two of them cold agglutinins. Such features have been previously described under the acronym “CANOMAD” (chronic ataxic neuropathy with ophthalmoplegia, M protein, agglutination and disialosyl antibodies).One of the patients presents extramembranous glomerulopathy and severe motor disability associated with this syndrome. The pathophysiology of the glomerulopathy seems to be linked with the polyneuropathy. Patients were treated either by intravenous immunoglobulin, corticosteroids or cyclophosphamid. Response to treatment differs in the three cases and there is currently no consensus.Our study demonstrates that spectrum of polyneuropathy associated with monoclonal polyneuropathy may be larger than originally described.

Journal of Parkinson's disease, Jan 16, 2015

Due to its high prevalence in dual-task paradigms, freezing of gait in Parkinson's disease is... more Due to its high prevalence in dual-task paradigms, freezing of gait in Parkinson's disease is thought to be associated with dysexecutive syndrome and attentional disorders. However, the role of specific attentional disorders in patients with freezing of gait is still unclear. Here, we sought to specifically determine which basic attentional modalities are impaired in patients with freezing of gait. Seventy-eight parkinsonian patients performed a computer-controlled reaction-time paradigm designed to measure the different attentional subcomponents, controlled for visuospatial processing and motor participation. The freezer (n = 42) and non-freezer (n = 36) groups were matched for age, educational level, MMSE and MDRS. There were no intergroup differences in simple reaction times, whereas choice reaction times were higher in the freezer group than in the non-freezer group for divided attention (p = 0.023). At equivalent levels of overall cognitive efficiency, freezer patients show...

Brain : a journal of neurology, Jan 23, 2015

After more than 50 years of treating Parkinson's disease with l-DOPA, there are still no guid... more After more than 50 years of treating Parkinson's disease with l-DOPA, there are still no guidelines on setting the optimal dose for a given patient. The dopamine transporter type 1, now known as solute carrier family 6 (neurotransmitter transporter), member 3 (SLC6A3) is the most powerful determinant of dopamine neurotransmission and might therefore influence the treatment response. We recently demonstrated that methylphenidate (a dopamine transporter inhibitor) is effective in patients with Parkinson's disease with motor and gait disorders. The objective of the present study was to determine whether genetic variants of the dopamine transporter type 1-encoding gene (SLC6A3) are associated with differences in the response to treatment of motor symptoms and gait disorders with l-DOPA and methylphenidate (with respect to the demographic, the disease and the treatment parameters and the other genes involved in the dopaminergic neurotransmission). This analysis was part of a mult...

Neuroscience letters, Jan 4, 2015

Falls frequently occur during daily activities such as reaching for an object in patients with Pa... more Falls frequently occur during daily activities such as reaching for an object in patients with Parkinson's disease (PD). Misjudgment is also reported to be one of the circumstances that lead to falls. The functional reach test is an indicator of dynamic balance. The primary objective was to establish whether there is a difference between self-perceived and actual ability to perform the functional reach test in patients with PD who have never fallen. Three groups of participants (all with no history of falls) were studied: young adults, elderly adults and PD patients. The participants first estimated their maximum reaching distance (but without performing the action, i.e. as a motor imagery task) and then actually performed the functional reach test (i.e. as a motor task). No significant overestimation or underestimation was observed. The reaching distance was lower in PD than in the two other groups. There were no differences between PD patients and elderly adults in terms of th...

Journal of Parkinson's disease, 2014

After several years duration of Parkinson's disease, with or without deep brain stimulation, ... more After several years duration of Parkinson's disease, with or without deep brain stimulation, axial signs (such as postural instability, freezing of gait) may worsen. High-voltage, low-frequency stimulation has been shown to improve severe gait disorders in some patients. To identify predictive factors for the efficacy of low-frequency stimulation. We assessed the respective effects of low- and high-frequency stimulation using an acute stand-walk- sit test, and on motor performance in 22 patients with longstanding, bilateral sub-thalamic nucleus stimulation. We calculated the difference in the number of steps (delta steps) between high and low -frequency stimulation during the stand-walk-sit test. Our aim was to establish a profile for low-frequency responders, which was defined by a positive value for delta steps. Low frequency responders presented higher age, a severe axial phenotype five years after surgery and a lower L-dopa responsiveness of (i) the Unified Parkinson's D...

Theriogenology, 1996

Nuclear transfer was used to study nuclear reprogramming of fetal diploid bovine germ cells colle... more Nuclear transfer was used to study nuclear reprogramming of fetal diploid bovine germ cells collected at two stages of the fetal development. In the first case, germ cells of both sexes were collected during their period of intragonadal mitotic multiplication at 48 days post coïtum (d.p.c.). In the second case, only male germ cells were collected after this period, between 105 and 185 d.p.c. Isolated germ cells were fused with enucleated oocytes. Reconstituted embryos were cultured in vitro and those reaching the compacted morula or blastocyst stage were transferred into synchronous recipient heifers. Of 511 reconstituted embryos with 48 d.p.c. germ cells (309 males and 202 females), 48% (247/511 ) cleaved; 2.7% (14/511 ) reached the compacted morula stage and 8 of them the blastocyst stage (1.6%). No difference was observed between sexes. All 14 compacted morulae/blastocysts were transferred into 6 recipients and one pregnancy was initiated. This recipient was slaughtered at Day 35...

Cognitive impairment without dementia is frequent in Parkinson&am... more Cognitive impairment without dementia is frequent in Parkinson's disease. It often presents as a dysexecutive syndrome with deficient attentional resource allocation. The nature of attention deficits in Parkinson's disease has rarely been investigated with robust, theory-based tasks. The main objective of the present study was to investigate attention disorders in Parkinson's disease patients by applying a paradigm based on a model of attention. We also sought to identify the main demographic and clinical characteristics associated with attention deficits in Parkinson's disease. Eighty non-demented Parkinson's disease patients and 60 healthy controls participated in the study. Attention was assessed in a computer-controlled reaction time paradigm. The test session comprised a simple reaction time task and four choice reaction time tasks: a go/no-go task, a one-dimension, focused-attention task, a two-dimension, divided-attention task and an alternating task. Performance was assessed by composite measures: (i) cognitive reaction time, corresponding to the difference between the simple reaction time and the choice reaction time in the given condition, and (ii) reaction time variability, corresponding to the sum of the coefficients of variance of the reaction times. Accuracy was also considered. Apart from an overall slowing and greater reaction time variability, Parkinson's disease patients were only significantly impaired in the alternating condition. This set-shifting impairment was associated with their performance in the go/no-go and divided-attention conditions. Our systematic assessment of the different attentional subcomponents revealed that mental flexibility is particularly impaired in non-demented Parkinson's disease patients.

Gait & Posture, 2014

Attentional resources appear to be involved in the occurrence of FoG. The Parkgait study recently... more Attentional resources appear to be involved in the occurrence of FoG. The Parkgait study recently reported that methylphenidate reduces gait hypokinesia and freezing of gait (FoG) in advanced PD patients receiving STN-DBS in the off-dopaminergic drug condition. Methylphenidate is considered to improve attention. The primary objective of the present ancillary study was to determine whether methylphenidate reduced the interference between a cognitive task and gait in patients with FoG. The study's secondary objective was to compare attentional performance in methylphenidate-treated and placebo-treated patients. A total of 24 patients (from two centers) were included in the study. Patients were randomly assigned 1:1 to a three-month course of methylphenidate (1mg/kg/day) or placebo. Patients were assessed after an acute L-dopa challenge. The primary outcome criterion was the stride length ratio ((dual-task stride length minus free gait stride length)/free gait stride length). Trials with FoG episodes were excluded from the analysis. Secondary outcomes included changes in reaction times for computerized attention tasks and FoG severity. When comparing patients receiving methylphenidate with those receiving placebo, we did not observe any significant differences in the interaction between the dual task and gait or in attentional performance. As in the main Parkgait study, methylphenidate did not reduce gait hypokinesia in patients receiving dopaminergic treatment. Our present results suggest that the reduction in the number of FoG episodes previously observed in patients on methylphenidate was neither due to interaction between a dual-task and gait nor an increase in attentional performance.

Neuroscience, 2011

The pathophysiology underlying freezing of gait (FOG) in Parkinson's disease remains incompletely... more The pathophysiology underlying freezing of gait (FOG) in Parkinson's disease remains incompletely understood. Patients with FOG ("freezers") have a higher temporal variability and asymmetry of strides compared to patients without FOG ("non-freezers"). We aimed to extend this view, by assessing spatial variability and asymmetry of steps and interlimb coordination between the upper and lower limbs during gait. Twelve freezers, 15 non-freezers, and 15 agematched controls were instructed to walk overground and on a treadmill. Kinematic data were recorded with a motion analysis system. Both freezers and non-freezers showed an increased spatial variability of leg movements compared to controls. In addition, both patient groups had a deficit in interlimb coordination, not only between ipsilateral arms and legs, but also between diagonally positioned limbs. The only difference between freezers and non-freezers was a decreased step length during treadmill walking. We conclude that parkinsonian gait-regardless of FOG-is irregular, not only in the legs, but also with respect to interlimb coordination between the arms and legs. FOG is reflected by abnormal treadmill walking, presumably because this provides a greater challenge to the defective supraspinal control than overground walking, hampering the ability of freezers to increase their stride length when necessary.

Freezing of gait (FOG) is a common axial symptom of Parkinson disease (PD). To determine the prev... more Freezing of gait (FOG) is a common axial symptom of Parkinson disease (PD). To determine the prevalence of FOG in a large group of PD patients, assess its relationship with quality of life and clinical and pharmacological factors, and explore its changes from the off to on conditions in patients with motor fluctuations. Cross-sectional survey of 683 patients with idiopathic PD. Scores for FOG were missing in 11 patients who were not included in the analysis. Patients were recruited from referral centers and general neurology clinics in public or private institutions in France. Patients with FOG were identified as those with a score of 1 or greater on item 14 of the Unified Parkinson's Disease Rating Scale (UPDRS) in the on condition. Item 14 scores for FOG in the off condition were also collected in patients with fluctuating motor symptoms. Quality of life (measured by the 39-item Parkinson's Disease Questionnaire and 36-Item Short Form Health Survey), anxiety and depression (Hospital Anxiety and Depression Scale), clinical features (UPDRS), and drug consumption. Of 672 PD patients, 257 reported FOG during the onstate (38.2%), which was significantly related to lower quality of life scores (P < .01). Freezing of gait was also correlated with longer PD duration (odds ratio, 1.92 [95% CI, 1.28-2.86]), higher UPDRS parts II and III scores (4.67 [3.21-6.78]), the presence of apathy (UPDRS item 4) (1.94 [1.33-2.82]), a higher levodopa equivalent daily dose (1.63 [1.09-2.43]), and more frequent exposure to antimuscarinics (3.07 [1.35-6.97]) (logistic regression). The FOG score improved from the off to on states in 148 of 174 patients with motor fluctuations (85.1%) and showed no change in 13.8%. The FOG score improved by more than 50% in 43.7% of patients. Greater improvement in the on state was observed in younger patients (r = -0.25; P < .01) with lower UPDRS II and III scores (r = -0.50; P < .01) and no antimuscarinic use (r = -0.21;…

Theriogenology, 1995

Embryo reconstruction by transplantation of 1 blastomem from an undifferentiated embryo into a ma... more Embryo reconstruction by transplantation of 1 blastomem from an undifferentiated embryo into a maturated and enucleated oocyte has been proposed as a means to obtain genetically identical animals. Due to various methodological (enucleation, electrofusion) or regulatory parameters (oocyte maturation, embryo development), the overall efficiency of the method is low. As mcloning constitutes a way to increase the number of embryos available for transfer, the aim of this work was to compare the rates of in vitro development and ongoing pregnancies after cloning and recloning.

Theriogenology, 1996

Sucrose (0.3 M) was used to cause artificial compaction of the embryonic cell mass of in vitro pr... more Sucrose (0.3 M) was used to cause artificial compaction of the embryonic cell mass of in vitro produced bovine embryos to facilitate morphological evaluation. Embryos were produced using routine in vitro maturation (IVM) and fertilization (IVF) techniques. The time necessary to induce shrinkage in 0.3 M sucrose to 75% of the original volume of Day 5 morulae was found to be less than l min, and 95% of the volume was regained in PBS after 2.5 min. No detrimental effect was observed after a 5- to 10-min sucrose treatment on subsequent blastocyst formation at Days 6 and 7 (P > 0.05). Furthermore, no significant differences were observed in the total number of cells, or in the mitotic and pycnotic cell index of blastocysts in different treatment groups. Agreement among 7 evaluators grading 40 Day 6 embryos was examined using the kappa coefficient of agreement (kappa). Overall agreement among evaluators for classification of quality grade was poor (48.2 %, kappa = 0.31) for embryos evaluated in PBS, but the rate improved when the same embryos were scored in sucrose (62.5 %, kappa = 0.49). Evaluating less compact in vitro produced bovine morulae in sucrose increases agreement among evaluators, since embryos in sucrose mimick the appearance of in vivo produced embryos. Thus, we conclude that scoring in vitro produced embryos in sucrose improves agreement among evaluators.

Theriogenology, 1993

Oocyte in vitro maturation and fertilization followed by in vitro embryo development are realized... more Oocyte in vitro maturation and fertilization followed by in vitro embryo development are realized in several laboratories. Generally, oocytes are obtained by aspiration of relatively large antral follicles (2-8 mm) present on the ovaries of slaughtered females. Ovaries are collected at random without any information on cow origin or on reproductive status. The aim of this study was to compare the embryo development of oocytes punctured from identified cows. The animals were originating from a single herd and were slaughtered by necessity. Females were classified as prepubertal, pregnant, cyclic with or without corpus luteum (CL). In order to maximize the number of oocytes, all follicles from 1 to 8 mm were punctured and oocytes selection was not as strict in normal working conditions; only the denuded and picnotic oocytes were discarded. In vitro maturation lasted 24-25 hours and was performed as described earlier (Theriogenology 37: 206, 1992). All fertilizations were done with the same belgian bull. Sperm selection was performed with a percoll-gradient and the gametes were co-incubated 16 hours in IVF-TALP.

Theriogenology, 1995

We described an exclusively in vitro procedure for cloning and recloning bovine embryos. Embryos ... more We described an exclusively in vitro procedure for cloning and recloning bovine embryos. Embryos obtained by IVM/IVF/IVC developed to the morula stage were used as blastomere donors in cunjunction with IVM recipient oocytes. Reconstructed embryos were developed in vitro in co-culture using bovine oviductal epithelial cells. The resulting morulae were used as donors for recloning under the same experimental conditions. No significant difference was observed between cloning and recloning in terms of development (rates of blastocysts: 12.9 versus 14.9%), in the number of nuclei per blastocyst (63.8 versus 49.1), or in pregnancy rates (35.7 versus 33.3%). The high variability observed between replicates and the correlation between results in first and second cycle nuclear transfer may suggest an inherant potential of individual donor embryos to support development by cloning.

Revue Neurologique, 2004

Les neuropathies périphériques associées à une gammapathie monoclonale de type IgM sont d’individ... more Les neuropathies périphériques associées à une gammapathie monoclonale de type IgM sont d’individualisation récente. Des autoanticorps sont susceptibles de réagir avec les glycoprotéines constitutives du nerf que ce soit la MAG (myelin associated protein) ou d’autres gangliosides contenant un acide sialique tels que le GM1, ou plusieurs acides sialiques tels que le GD3, le GD1b, le GT1b, le GQ1b.Nous décrivons trois cas de patients présentant des troubles oculomoteurs, une neuropathie sensitive ataxiante chronique, une vitesse de sédimentation élevée, une gammapathie monoclonale de type IgM, des anticorps anti-gangliosides disialylés, et la présence d’agglutinines froides réalisant un syndrome de type « CANOMAD » pour « chronic ataxic neuropathy with ophtalmoplegia, M protein, agglutination and disialosyl antibodies ».Un des cas était associé à une glomérulopathie de type extramembraneuse et à une atteinte motrice sévère. La physiopathologie de cette glomérulopathie apparaît liée à la polyneuropathie. La réponse des patients aux différents traitements (corticothérapie, immunoglobulines polyvalentes, cyclophosphamide) ne permet pas d’établir de consensus thérapeutique à ce jour.Cette étude montre que le spectre de ces neuropathies associées à une dysglobulinémie apparaît plus large que celui décrit initialement.Polyneuropathies associated with IgM monoclonal gammopathy were recently recognized. Antibodies can react with glycoproteins such as myelin associated glycoprotein (MAG), or gangliosides containing one sialosyl epitope such as GM1 or several sialosyl epitopes (polysialyted gangliosides) including GD2, GD3, GT1b, GT1a, GQ1b.We report on three patients presenting oculomotor dysfunction, chronic sensitive ataxic polyneuropathy, high sedimentation rate, IgM monoclonal paraprotein of unknown signification and antidisialosyl IgM antibodies and for two of them cold agglutinins. Such features have been previously described under the acronym “CANOMAD” (chronic ataxic neuropathy with ophthalmoplegia, M protein, agglutination and disialosyl antibodies).One of the patients presents extramembranous glomerulopathy and severe motor disability associated with this syndrome. The pathophysiology of the glomerulopathy seems to be linked with the polyneuropathy. Patients were treated either by intravenous immunoglobulin, corticosteroids or cyclophosphamid. Response to treatment differs in the three cases and there is currently no consensus.Our study demonstrates that spectrum of polyneuropathy associated with monoclonal polyneuropathy may be larger than originally described.

Journal of Parkinson's disease, Jan 16, 2015

Due to its high prevalence in dual-task paradigms, freezing of gait in Parkinson's disease is... more Due to its high prevalence in dual-task paradigms, freezing of gait in Parkinson's disease is thought to be associated with dysexecutive syndrome and attentional disorders. However, the role of specific attentional disorders in patients with freezing of gait is still unclear. Here, we sought to specifically determine which basic attentional modalities are impaired in patients with freezing of gait. Seventy-eight parkinsonian patients performed a computer-controlled reaction-time paradigm designed to measure the different attentional subcomponents, controlled for visuospatial processing and motor participation. The freezer (n = 42) and non-freezer (n = 36) groups were matched for age, educational level, MMSE and MDRS. There were no intergroup differences in simple reaction times, whereas choice reaction times were higher in the freezer group than in the non-freezer group for divided attention (p = 0.023). At equivalent levels of overall cognitive efficiency, freezer patients show...

Brain : a journal of neurology, Jan 23, 2015

After more than 50 years of treating Parkinson's disease with l-DOPA, there are still no guid... more After more than 50 years of treating Parkinson's disease with l-DOPA, there are still no guidelines on setting the optimal dose for a given patient. The dopamine transporter type 1, now known as solute carrier family 6 (neurotransmitter transporter), member 3 (SLC6A3) is the most powerful determinant of dopamine neurotransmission and might therefore influence the treatment response. We recently demonstrated that methylphenidate (a dopamine transporter inhibitor) is effective in patients with Parkinson's disease with motor and gait disorders. The objective of the present study was to determine whether genetic variants of the dopamine transporter type 1-encoding gene (SLC6A3) are associated with differences in the response to treatment of motor symptoms and gait disorders with l-DOPA and methylphenidate (with respect to the demographic, the disease and the treatment parameters and the other genes involved in the dopaminergic neurotransmission). This analysis was part of a mult...

Neuroscience letters, Jan 4, 2015

Falls frequently occur during daily activities such as reaching for an object in patients with Pa... more Falls frequently occur during daily activities such as reaching for an object in patients with Parkinson's disease (PD). Misjudgment is also reported to be one of the circumstances that lead to falls. The functional reach test is an indicator of dynamic balance. The primary objective was to establish whether there is a difference between self-perceived and actual ability to perform the functional reach test in patients with PD who have never fallen. Three groups of participants (all with no history of falls) were studied: young adults, elderly adults and PD patients. The participants first estimated their maximum reaching distance (but without performing the action, i.e. as a motor imagery task) and then actually performed the functional reach test (i.e. as a motor task). No significant overestimation or underestimation was observed. The reaching distance was lower in PD than in the two other groups. There were no differences between PD patients and elderly adults in terms of th...

Journal of Parkinson's disease, 2014

After several years duration of Parkinson's disease, with or without deep brain stimulation, ... more After several years duration of Parkinson's disease, with or without deep brain stimulation, axial signs (such as postural instability, freezing of gait) may worsen. High-voltage, low-frequency stimulation has been shown to improve severe gait disorders in some patients. To identify predictive factors for the efficacy of low-frequency stimulation. We assessed the respective effects of low- and high-frequency stimulation using an acute stand-walk- sit test, and on motor performance in 22 patients with longstanding, bilateral sub-thalamic nucleus stimulation. We calculated the difference in the number of steps (delta steps) between high and low -frequency stimulation during the stand-walk-sit test. Our aim was to establish a profile for low-frequency responders, which was defined by a positive value for delta steps. Low frequency responders presented higher age, a severe axial phenotype five years after surgery and a lower L-dopa responsiveness of (i) the Unified Parkinson's D...

Theriogenology, 1996

Nuclear transfer was used to study nuclear reprogramming of fetal diploid bovine germ cells colle... more Nuclear transfer was used to study nuclear reprogramming of fetal diploid bovine germ cells collected at two stages of the fetal development. In the first case, germ cells of both sexes were collected during their period of intragonadal mitotic multiplication at 48 days post coïtum (d.p.c.). In the second case, only male germ cells were collected after this period, between 105 and 185 d.p.c. Isolated germ cells were fused with enucleated oocytes. Reconstituted embryos were cultured in vitro and those reaching the compacted morula or blastocyst stage were transferred into synchronous recipient heifers. Of 511 reconstituted embryos with 48 d.p.c. germ cells (309 males and 202 females), 48% (247/511 ) cleaved; 2.7% (14/511 ) reached the compacted morula stage and 8 of them the blastocyst stage (1.6%). No difference was observed between sexes. All 14 compacted morulae/blastocysts were transferred into 6 recipients and one pregnancy was initiated. This recipient was slaughtered at Day 35...

Cognitive impairment without dementia is frequent in Parkinson&am... more Cognitive impairment without dementia is frequent in Parkinson's disease. It often presents as a dysexecutive syndrome with deficient attentional resource allocation. The nature of attention deficits in Parkinson's disease has rarely been investigated with robust, theory-based tasks. The main objective of the present study was to investigate attention disorders in Parkinson's disease patients by applying a paradigm based on a model of attention. We also sought to identify the main demographic and clinical characteristics associated with attention deficits in Parkinson's disease. Eighty non-demented Parkinson's disease patients and 60 healthy controls participated in the study. Attention was assessed in a computer-controlled reaction time paradigm. The test session comprised a simple reaction time task and four choice reaction time tasks: a go/no-go task, a one-dimension, focused-attention task, a two-dimension, divided-attention task and an alternating task. Performance was assessed by composite measures: (i) cognitive reaction time, corresponding to the difference between the simple reaction time and the choice reaction time in the given condition, and (ii) reaction time variability, corresponding to the sum of the coefficients of variance of the reaction times. Accuracy was also considered. Apart from an overall slowing and greater reaction time variability, Parkinson's disease patients were only significantly impaired in the alternating condition. This set-shifting impairment was associated with their performance in the go/no-go and divided-attention conditions. Our systematic assessment of the different attentional subcomponents revealed that mental flexibility is particularly impaired in non-demented Parkinson's disease patients.

Gait & Posture, 2014

Attentional resources appear to be involved in the occurrence of FoG. The Parkgait study recently... more Attentional resources appear to be involved in the occurrence of FoG. The Parkgait study recently reported that methylphenidate reduces gait hypokinesia and freezing of gait (FoG) in advanced PD patients receiving STN-DBS in the off-dopaminergic drug condition. Methylphenidate is considered to improve attention. The primary objective of the present ancillary study was to determine whether methylphenidate reduced the interference between a cognitive task and gait in patients with FoG. The study's secondary objective was to compare attentional performance in methylphenidate-treated and placebo-treated patients. A total of 24 patients (from two centers) were included in the study. Patients were randomly assigned 1:1 to a three-month course of methylphenidate (1mg/kg/day) or placebo. Patients were assessed after an acute L-dopa challenge. The primary outcome criterion was the stride length ratio ((dual-task stride length minus free gait stride length)/free gait stride length). Trials with FoG episodes were excluded from the analysis. Secondary outcomes included changes in reaction times for computerized attention tasks and FoG severity. When comparing patients receiving methylphenidate with those receiving placebo, we did not observe any significant differences in the interaction between the dual task and gait or in attentional performance. As in the main Parkgait study, methylphenidate did not reduce gait hypokinesia in patients receiving dopaminergic treatment. Our present results suggest that the reduction in the number of FoG episodes previously observed in patients on methylphenidate was neither due to interaction between a dual-task and gait nor an increase in attentional performance.

Neuroscience, 2011

The pathophysiology underlying freezing of gait (FOG) in Parkinson's disease remains incompletely... more The pathophysiology underlying freezing of gait (FOG) in Parkinson's disease remains incompletely understood. Patients with FOG ("freezers") have a higher temporal variability and asymmetry of strides compared to patients without FOG ("non-freezers"). We aimed to extend this view, by assessing spatial variability and asymmetry of steps and interlimb coordination between the upper and lower limbs during gait. Twelve freezers, 15 non-freezers, and 15 agematched controls were instructed to walk overground and on a treadmill. Kinematic data were recorded with a motion analysis system. Both freezers and non-freezers showed an increased spatial variability of leg movements compared to controls. In addition, both patient groups had a deficit in interlimb coordination, not only between ipsilateral arms and legs, but also between diagonally positioned limbs. The only difference between freezers and non-freezers was a decreased step length during treadmill walking. We conclude that parkinsonian gait-regardless of FOG-is irregular, not only in the legs, but also with respect to interlimb coordination between the arms and legs. FOG is reflected by abnormal treadmill walking, presumably because this provides a greater challenge to the defective supraspinal control than overground walking, hampering the ability of freezers to increase their stride length when necessary.

Freezing of gait (FOG) is a common axial symptom of Parkinson disease (PD). To determine the prev... more Freezing of gait (FOG) is a common axial symptom of Parkinson disease (PD). To determine the prevalence of FOG in a large group of PD patients, assess its relationship with quality of life and clinical and pharmacological factors, and explore its changes from the off to on conditions in patients with motor fluctuations. Cross-sectional survey of 683 patients with idiopathic PD. Scores for FOG were missing in 11 patients who were not included in the analysis. Patients were recruited from referral centers and general neurology clinics in public or private institutions in France. Patients with FOG were identified as those with a score of 1 or greater on item 14 of the Unified Parkinson's Disease Rating Scale (UPDRS) in the on condition. Item 14 scores for FOG in the off condition were also collected in patients with fluctuating motor symptoms. Quality of life (measured by the 39-item Parkinson's Disease Questionnaire and 36-Item Short Form Health Survey), anxiety and depression (Hospital Anxiety and Depression Scale), clinical features (UPDRS), and drug consumption. Of 672 PD patients, 257 reported FOG during the onstate (38.2%), which was significantly related to lower quality of life scores (P < .01). Freezing of gait was also correlated with longer PD duration (odds ratio, 1.92 [95% CI, 1.28-2.86]), higher UPDRS parts II and III scores (4.67 [3.21-6.78]), the presence of apathy (UPDRS item 4) (1.94 [1.33-2.82]), a higher levodopa equivalent daily dose (1.63 [1.09-2.43]), and more frequent exposure to antimuscarinics (3.07 [1.35-6.97]) (logistic regression). The FOG score improved from the off to on states in 148 of 174 patients with motor fluctuations (85.1%) and showed no change in 13.8%. The FOG score improved by more than 50% in 43.7% of patients. Greater improvement in the on state was observed in younger patients (r = -0.25; P < .01) with lower UPDRS II and III scores (r = -0.50; P < .01) and no antimuscarinic use (r = -0.21;…

Theriogenology, 1995

Embryo reconstruction by transplantation of 1 blastomem from an undifferentiated embryo into a ma... more Embryo reconstruction by transplantation of 1 blastomem from an undifferentiated embryo into a maturated and enucleated oocyte has been proposed as a means to obtain genetically identical animals. Due to various methodological (enucleation, electrofusion) or regulatory parameters (oocyte maturation, embryo development), the overall efficiency of the method is low. As mcloning constitutes a way to increase the number of embryos available for transfer, the aim of this work was to compare the rates of in vitro development and ongoing pregnancies after cloning and recloning.

Theriogenology, 1996

Sucrose (0.3 M) was used to cause artificial compaction of the embryonic cell mass of in vitro pr... more Sucrose (0.3 M) was used to cause artificial compaction of the embryonic cell mass of in vitro produced bovine embryos to facilitate morphological evaluation. Embryos were produced using routine in vitro maturation (IVM) and fertilization (IVF) techniques. The time necessary to induce shrinkage in 0.3 M sucrose to 75% of the original volume of Day 5 morulae was found to be less than l min, and 95% of the volume was regained in PBS after 2.5 min. No detrimental effect was observed after a 5- to 10-min sucrose treatment on subsequent blastocyst formation at Days 6 and 7 (P > 0.05). Furthermore, no significant differences were observed in the total number of cells, or in the mitotic and pycnotic cell index of blastocysts in different treatment groups. Agreement among 7 evaluators grading 40 Day 6 embryos was examined using the kappa coefficient of agreement (kappa). Overall agreement among evaluators for classification of quality grade was poor (48.2 %, kappa = 0.31) for embryos evaluated in PBS, but the rate improved when the same embryos were scored in sucrose (62.5 %, kappa = 0.49). Evaluating less compact in vitro produced bovine morulae in sucrose increases agreement among evaluators, since embryos in sucrose mimick the appearance of in vivo produced embryos. Thus, we conclude that scoring in vitro produced embryos in sucrose improves agreement among evaluators.

Theriogenology, 1993

Oocyte in vitro maturation and fertilization followed by in vitro embryo development are realized... more Oocyte in vitro maturation and fertilization followed by in vitro embryo development are realized in several laboratories. Generally, oocytes are obtained by aspiration of relatively large antral follicles (2-8 mm) present on the ovaries of slaughtered females. Ovaries are collected at random without any information on cow origin or on reproductive status. The aim of this study was to compare the embryo development of oocytes punctured from identified cows. The animals were originating from a single herd and were slaughtered by necessity. Females were classified as prepubertal, pregnant, cyclic with or without corpus luteum (CL). In order to maximize the number of oocytes, all follicles from 1 to 8 mm were punctured and oocytes selection was not as strict in normal working conditions; only the denuded and picnotic oocytes were discarded. In vitro maturation lasted 24-25 hours and was performed as described earlier (Theriogenology 37: 206, 1992). All fertilizations were done with the same belgian bull. Sperm selection was performed with a percoll-gradient and the gametes were co-incubated 16 hours in IVF-TALP.

Theriogenology, 1995

We described an exclusively in vitro procedure for cloning and recloning bovine embryos. Embryos ... more We described an exclusively in vitro procedure for cloning and recloning bovine embryos. Embryos obtained by IVM/IVF/IVC developed to the morula stage were used as blastomere donors in cunjunction with IVM recipient oocytes. Reconstructed embryos were developed in vitro in co-culture using bovine oviductal epithelial cells. The resulting morulae were used as donors for recloning under the same experimental conditions. No significant difference was observed between cloning and recloning in terms of development (rates of blastocysts: 12.9 versus 14.9%), in the number of nuclei per blastocyst (63.8 versus 49.1), or in pregnancy rates (35.7 versus 33.3%). The high variability observed between replicates and the correlation between results in first and second cycle nuclear transfer may suggest an inherant potential of individual donor embryos to support development by cloning.