Gait disorders and axial symptoms are the main therapeutic challenges in advanced Parkinson's disease (PD). Gait disorders in PD are characterized by spatial and temporal dysfunction. Gait hypokinesia is the first to appear and is... more
Gait disorders and axial symptoms are the main therapeutic challenges in advanced Parkinson's disease (PD). Gait disorders in PD are characterized by spatial and temporal dysfunction. Gait hypokinesia is the first to appear and is responsible for the decrease in velocity. A good sensitivity to the levodopa is well established. Morris et al. [Morris ME, Iansek R, Matyas TA, Summers JJ. Ability to modulate walking cadence remains intact in Parkinson's disease. J Neurol Neurosurg Psychiatry 1994a;57(12):1532-4; Morris ME, Iansek R, Matyas TA, Summers JJ. The pathogenesis of gait hypokinesia in Parkinson's disease. Brain 1994b;117(Pt. 5):1169-81; Morris ME, Iansek R, Matyas TA, Summers JJ. Stride length regulation in Parkinson's disease. Brain 1996;119:551-68] demonstrated that the ability to modulate walking cadence remains intact in PD, and could correspond to a compensatory mechanism. More advanced disease stages of the disease are characterized by abnormal temporal p...
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Research Interests: Cognitive Science, Magnetic Resonance Imaging, Kidney transplantation, Coma, Humans, and 13 moreMale, Young Adult, Cyclosporine, Prednisolone, Anti-inflammatory agents, Levodopa, Clinical Sciences, West nile virus, Immunocompromised host, West Nile Fever, Meningoencephalitis, Enzyme Linked Immunosorbent Assay, and immunoglobulin G
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of upper and lower motorneurons, leading to death in 3 to 5 years. Respiratory insufficiency and hypoxemia are closely linked during the clinical course of ALS. Chronic... more
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of upper and lower motorneurons, leading to death in 3 to 5 years. Respiratory insufficiency and hypoxemia are closely linked during the clinical course of ALS. Chronic respiratory insufficiency and hypoxemia generally occur late in the disease course but rapid episodes of intermittent hypoxemia followed by reoxygenation can occur early and insidiously. Two pathways are involved in the response to hypoxemia: (i) hypoxia inducible factor-1 (HIF-1) and VEGF/HIF-2 and an erythropoietin (EPO) mediated pathway, in response to prolonged hypoxemia; and (ii) nuclear factor kappa-B (NFkappa-B) during acute hypoxemia followed by reoxygenation episodes, inducing inflammatory mediators: interleukin-6 (IL-6), TNF-alpha, cyclo oxygenase-2 (COX-2) and prostaglandin E-2 (PGE-2). Our aim was to specify the role of the different functional pathways of response to hypoxemia in sporadic ALS patients, compared with neurological controls...
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Growing body of evidence suggests that Parkinson's disease (PD) is associated with oxidative damage via iron accumulation in the substantia nigra (SN). Low ceruloplasmin (CP)-ferroxidase activity has been identified in the SN and the... more
Growing body of evidence suggests that Parkinson's disease (PD) is associated with oxidative damage via iron accumulation in the substantia nigra (SN). Low ceruloplasmin (CP)-ferroxidase activity has been identified in the SN and the cerebrospinal fluid (CSF) of patients with PD. The iron chelator, deferiprone, reduces the abnormally high levels of iron in the SN. In order to determine CP's involvement in iron accumulation in SN and PD progression, we aim to compare the ability of iron chelation treatment to reducing both SN iron levels and motor handicap in PD patients according to the level of ceruloplasmin activity. We used a moderate chelation protocol with deferiprone (DFP) based on a, 6-month delayed-start paradigm, randomized placebo controlled clinical trial in 40 PD patients. CP-ferroxidase activity was determined in blood and CSF together with the D544E gene polymorphism (rs701753). Iron levels were determined by R2* MRI sequence and the motor handicap by the UPDRS...
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To describe contraceptive practices of men in a relationship in France, where use of female-controlled methods is predominant, and to explore their involvement in managing contraception within the couple. Data are drawn from a national... more
To describe contraceptive practices of men in a relationship in France, where use of female-controlled methods is predominant, and to explore their involvement in managing contraception within the couple. Data are drawn from a national probability cross-sectional survey on sexual and reproductive health conducted in France in 2010. The study sample comprised 3,373 men aged 15-49, 1,776 of whom of whom were asked about their current contraceptive practices after they reported they were fecund and sexually active and did not currently want a child. Analyses were performed with logistic regression models. Few men aged 15-49 with a partner did not use contraception (3.4%). Most reported using only a female method (71.7%), 20.4% only cooperative methods, such as condoms, withdrawal, and the rhythm method, and 4.5% both. Among contraceptive users, withdrawal (7.7%) was more likely to be used by men with low incomes or low educational levels. Condom use was reported as a contraceptive meth...
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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... 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...
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Despite recent studies showing evidence that the organisation of the French health care system raises some problems concerning access to abortion, far little is known on the reality of access conditions and the views of women on the... more
Despite recent studies showing evidence that the organisation of the French health care system raises some problems concerning access to abortion, far little is known on the reality of access conditions and the views of women on the difficulties they experience when they attend an abortion clinic. In this article, we discuss the complementarity of materials from two surveys one qualitative, the other quantitative in the study of patterns of care for an abortion. The qualitative survey included 51 women who reported a history of induced abortion, selected from a qualitative study on unintended pregnancy in France. The quantitative survey included 480 women, who had an abortion in the past 10 years. These women were selected from a representative sample of 2863 women aged 18 to 44, who participated in a study on contraception and abortion. The variety of patterns of care for an abortion, the rareness of dysfunctions in the health care system and the importance of the first professiona...
Research Interests: Social Support, Adolescent, France, Pregnancy, Humans, and 4 moreFemale, Questionnaires, Adult, and Age Factors
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Research Interests: Demography, Research Methodology, Mental Health, Behavior, Health, and 16 moreAdolescent, France, Population, Humans, Measurement, Female, Patient Compliance, Patient Satisfaction, Incidence, Developed Countries, Questionnaires, Adult, Sex Factors, Logistic Models, Oral Contraceptive, and Socioeconomic Factors
Autosomal dominant cerebellar ataxia corresponds to a clinically and genetically heterogeneous group of neurodegenerative disorders that primarily affect the cerebellum. Here, we report the identification of the causative gene in... more
Autosomal dominant cerebellar ataxia corresponds to a clinically and genetically heterogeneous group of neurodegenerative disorders that primarily affect the cerebellum. Here, we report the identification of the causative gene in spinocerebellar ataxia 21, an autosomal-dominant disorder previously mapped to chromosome 7p21.3-p15.1. This ataxia was firstly characterized in a large French family with slowly progressive cerebellar ataxia, accompanied by severe cognitive impairment and mental retardation in two young children. Following the recruitment of 12 additional young family members, linkage analysis enabled us to definitively map the disease locus to chromosome 1p36.33-p36.32. The causative mutation, (c.509C>T/p.P170L) in the transmembrane protein gene TMEM240, was identified by whole exome sequencing and then was confirmed by Sanger sequencing and co-segregation analyses. Index cases from 368 French families with autosomal-dominant cerebellar ataxia were also screened for mu...
Research Interests: Membrane Proteins, Adolescent, Intellectual Disability, France, Brain, and 17 moreHumans, Child, Mutation, Female, Male, Polymerase Chain Reaction, Young Adult, Infant, Pedigree, Genetic linkage analysis, Introns, Intelligence tests, Amino Acid Sequence, Age of Onset, Cognition disorders, Exome, and Cohort Studies
ABSTRACT La sclérose latérale amyotrophique (SLA) est une maladie neurodégénérative incurable, grave (médiane de survie de 24 mois après diagnostic), caractérisée par un dysfonctionnement rapidement progressif des motoneurones centraux et... more
ABSTRACT La sclérose latérale amyotrophique (SLA) est une maladie neurodégénérative incurable, grave (médiane de survie de 24 mois après diagnostic), caractérisée par un dysfonctionnement rapidement progressif des motoneurones centraux et périphériques. Les formes cliniques diffèrent selon la localisation initiale du déficit moteur, la vitesse de la perte neuronale, le retentissement fonctionnel, et l’association ou non à des troubles psycho-comportementaux ou cognitifs. Le pronostic vital est conditionné par l’atteinte respiratoire et l’état nutritionnel. Il peut être amélioré par la mise en place rapide de toutes les stratégies thérapeutiques permettant de corriger les troubles nutritionnels, de compenser les troubles respiratoires, en particulier ceux du sommeil, de prévenir les fausses routes alimentaires, les chutes et les infections respiratoires, en respectant la volonté du malade. Une bonne collaboration du malade et de ses proches est nécessaire : elle dépend de la qualité de l’annonce du diagnostic et des informations faites par les médecins en veillant à respecter les mécanismes psychologiques d’adaptation à une maladie très anxiogène. La qualité de vie dépend des aides à la lutte contre le handicap et du soutien psychosocial adaptés à l’évolution de la maladie, en évoquant les problèmes pratiques du quotidien et la charge pour les proches, en particulier le conjoint qui est souvent le principal et parfois l’unique aidant naturel du malade. Cela demande une grande disponibilité des équipes soignantes et l’intervention coordonnée de professionnels de compétences complémentaires à l’hôpital comme au domicile : la lutte contre le handicap, la pneumologie, la nutrition, la psychologie et les soins palliatifs. La prise en charge de la phase avancée de la SLA (où la dépendance est totale et où l’atteinte respiratoire et l’état nutritionnel menacent la vie) soulève des questions éthiques difficiles sur l’autonomie décisionnelle du malade et la bienfaisance des traitements invasifs de soutien de la vie, en particulier la ventilation mécanique sur trachéotomie.
Plasma and CSF from patients with ALS and control subjects were obtained with informed consent as part of the diagnostic evaluation or a research protocol (table). Neurologic controls included degenerative disorders: Parkinson disease... more
Plasma and CSF from patients with ALS and control subjects were obtained with informed consent as part of the diagnostic evaluation or a research protocol (table). Neurologic controls included degenerative disorders: Parkinson disease (PD), supranuclear palsy, hydrocephaly, ...
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In accordance with the principle of personal autonomy, expert consensus statements on amyotrophic lateral sclerosis (ALS) recommend early engagement with terminal-phase patients on the type of symptomatic treatment to be administered in... more
In accordance with the principle of personal autonomy, expert consensus statements on amyotrophic lateral sclerosis (ALS) recommend early engagement with terminal-phase patients on the type of symptomatic treatment to be administered in the event of respiratory failure, since decompensation progresses too rapidly to allow time for a discussion. The French Parliamentary Act on Patients' Rights and End-of-Life Care (dated 22 April 2005) grants individuals the right to refuse unreasonable treatment and obliges physicians to take account of any prior instructions given by a person before he/she became incapable of communicating. The provision of prior instructions is a very reassuring situation for the physician: the autonomous patient indicates his or her choice of end-of-life care. However, there are two pitfalls which must be avoided: (i) holding a discussion for the sole purpose of obtaining prior instructions and (ii) not acknowledging the patient's vulnerability. The present study dealt with 35 ALS patients for whom the question of either intensive care or palliative end-of-life care remained open. Even though the great majority of these individuals were keen to know their exact state of health, 48% refused to consider this circumstance and only 20% expressed prior instructions. These results prompted us to question the ethical dimension of the concept of autonomy beyond its founding formulation: can one envisage an incapacity to confront oneself with the existential question of possible death? In 80% of cases, the physician will have to take a care decision in the absence of any prior instructions from the patient. This amounts to more than respecting a person's autonomy and involves exercising medical responsibility.
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Continuous subcutaneous infusion of apomorphine (CAI) has shown efficacy in the treatment of motor fluctuations but its place in the therapeutic arsenal remains poorly defined in terms of indication, acceptability and long-term tolerance.... more
Continuous subcutaneous infusion of apomorphine (CAI) has shown efficacy in the treatment of motor fluctuations but its place in the therapeutic arsenal remains poorly defined in terms of indication, acceptability and long-term tolerance. Indeed, few studies have been carried out with a follow-up greater than 12 months. The main objective was to assess the quality of life of Parkinson's disease (PD) patients treated with CAI. We also evaluate the effectiveness on the motor fluctuations, the long-term tolerance of this treatment with its causes of discontinuation and the treatment regimens used. We conducted a retrospective study of 81 PD patients treated with CAI between April 2003 and June 2012. Data were collected from medical records. A repeated measures analysis of variance by the linear mixed model was used (significance level: 5%). In August 2012, 27/81 patients were still treated with CAI with a mean duration of 28 months, 46/81 discontinued CAI (9 precociously), and 8 were lost to view. We didn't show improvement in the quality of life nor efficacy of CAI on the UPDRS IV score (P=0.54) and dyskinesia score (P=0.95). The CGI score patient also reflects this result with a majority response suggesting no significant change with CAI. We observed relative good cognitive and psychiatric tolerance. Adverse events were frequent but often benign. The average (±SD) rate of apomorphine was 3.15±1.71 mg/h and the oral dopaminergic treatment was decreased by 37.8%. The results are consistent with the literature except for the lack of efficiency on motor fluctuations which may be due to the use of too small doses of apomorphine. This seems to be a leading cause of discontinuation of CAI, especially when it is associated with side effects or important constraints. For better efficiency on motor fluctuations, we recommend the use of apomorphine at higher doses to obtain an optimal continuous dopaminergic stimulation.
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Research Interests: Cognitive Science, Magnetic Resonance Imaging, Kidney transplantation, Coma, Humans, and 13 moreMale, Young Adult, Cyclosporine, Prednisolone, Anti-inflammatory agents, Levodopa, Clinical Sciences, West nile virus, Immunocompromised host, West Nile Fever, Meningoencephalitis, Enzyme Linked Immunosorbent Assay, and immunoglobulin G
Research Interests: Engineering, Algorithms, Physics, Chemistry, Principal Component Analysis, and 26 moreBiology, Metabolomics, NMR Spectroscopy, Magnetic Resonance Spectroscopy, Medicine, Multidisciplinary, Quantitative analysis, Amyotrophic Lateral Sclerosis, Discriminant Analysis, Humans, Glucose Metabolism, Female, Male, PLoS one, Aged, Middle Aged, Ascorbic Acid, Adult, Neurodegenerative Disease, Amino Acid Profile, Quantitative Analysis, Protons, Early Diagnosis, Organic Acid, Case Control Studies, and Nuclear Magnetic Resonance Spectroscopy
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An understanding of the association between adolescents' sexual and reproductive health knowledge and their use of relevant services is needed to improve young... more
An understanding of the association between adolescents' sexual and reproductive health knowledge and their use of relevant services is needed to improve young people's sexual and reproductive health. Data from the National Survey of Family Growth were used to examine associations between sexual and reproductive health communication (parental and formal) and service use among 2,326 U.S. women aged 15-19 in 2002 and 2006-2008. Chi-square tests and multivariate logistic regression were used to assess relationships between adolescents' receipt of sexual and reproductive health communication from parents and formal (school, church, community) sources and their use of sexual and reproductive health services. The majority of adolescents had received parental (75%) and formal (92%) sexual and reproductive health communication; 43% reported recent service use. In unadjusted analyses, parental and formal communication were positively associated with service use. In regression models, overall parental communication remained positively associated with service use (odds ratio, 1.6); parental abstinence-only communication, which was not significant in 2002, was associated with reduced odds of service use for the pooled sample (0.4) and in 2006-2008 (0.3). Formal communication was not associated with service use. Further research is needed to assess whether comprehensive sexual and reproductive health communication facilitates adolescents' health care utilization. Examination of how communication sources, quality and content are related to service use is needed to understand adolescents' sexual and reproductive health knowledge and needs.
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Research Interests: Adolescent, Humans, Child, Female, Male, and 5 moreYoung Adult, Infant, Cerebellar ataxia, Phenotype, and Adult
1. N Engl J Med. 2009 Feb 26;360(9):935-6; author reply 936. Levodopa for Parkinson's disease. Devos D, Moreau C, Destée A. Comment on: N Engl J Med. 2008 Dec 4;359(23):2468-76. PMID: 19246370 [PubMed - indexed for MEDLINE]... more
1. N Engl J Med. 2009 Feb 26;360(9):935-6; author reply 936. Levodopa for Parkinson's disease. Devos D, Moreau C, Destée A. Comment on: N Engl J Med. 2008 Dec 4;359(23):2468-76. PMID: 19246370 [PubMed - indexed for MEDLINE] Publication Types: Comment; Letter. ...
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The clinical course of the degenerative motor neuron disorder amyotrophic lateral sclerosis (ALS) is closely related to hypoxia. The normal response to hypoxia involves two pathways in particular: the hypoxia inducible factor 1α (HIF-1α)... more
The clinical course of the degenerative motor neuron disorder amyotrophic lateral sclerosis (ALS) is closely related to hypoxia. The normal response to hypoxia involves two pathways in particular: the hypoxia inducible factor 1α (HIF-1α) pathway (which notably controls the synthesis of vascular endothelial growth factor (VEGF)) and the nuclear factor kappa B (NF-κb) pathway (responsible for the production of inflammatory mediators, including prostaglandin E2 (PGE2)). Defects in VEGF gene expression are known to cause motor neuron degeneration in animal models. Circulating monocytes are precursors of the microglia, which are involved in the pathogenesis of ALS. To establish whether the HIF-1 and/or NF-κB pathways are deregulated during hypoxia in early-stage, sporadic ALS, we analyzed the response to acute (1 h) and prolonged (24 h) hypoxia in monocytes from ALS and healthy controls. We measured protein expression and mRNA transcription for VEGF, HIF-1, HIF-2, prolyl hydroxylases 1 and 2 (PHD-1 and -2, part of the HIF proteasome-dependent degradation pathway) and their modulation by PGE2. Our results showed that (i) the HIF-1 (but not HIF-2) and VEGF production induced by acute and prolonged hypoxia was selectively and markedly altered in ALS patients and (ii) this defect was not compensated for by PGE2 addition. Moreover, altered HIF-1α activation was associated with low levels of proteolysis by PHD-2 in cells from sporadic ALS patients (relative to controls). For the first time, we have demonstrated clinical and functional abnormalities in the HIF-1 pathway during hypoxia in monocytes from sporadic ALS patients.
Research Interests: Neuroscience, Psychology, Motor neuron, Gene expression, Signal Transduction, and 18 moreAmyotrophic Lateral Sclerosis, Peroxidase, Humans, Anoxia, Female, Microglia, Male, Animal Model, Aged, Middle Aged, Monocytes, Degeneration, Protein Expression, Neurosciences, Prostaglandin E2, nuclear factor kappa B, Vascular Endothelial Growth Factor, and Down-Regulation
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Research Interests: Animal Studies, Amyotrophic Lateral Sclerosis, Erythropoietin, Cerebrospinal Fluid, Humans, and 16 moreAnoxia, Female, Male, Arterial Blood Pressure, Medical Physiology, Transcription Factor, Clinical Sciences, Aged, Middle Aged, Adult, Neuromuscular Disorders, Growth Factor, Oxygen Consumption, Neurosciences, Oxygen saturation, and Vascular Endothelial Growth Factor
Parkinsonian dysarthria (as typically characterized by hypophonia, monotony of pitch, and rhythm abnormalities) is often accompanied by gait disturbances. The long-term effect of subthalamic nucleus deep brain stimulation (STN DBS) on... more
Parkinsonian dysarthria (as typically characterized by hypophonia, monotony of pitch, and rhythm abnormalities) is often accompanied by gait disturbances. The long-term effect of subthalamic nucleus deep brain stimulation (STN DBS) on dysarthria remains unclear. Given STN DBS's known improvement of gait disorders, we analyzed speech intelligibility and aerodynamic and acoustic parameters in 11 advanced PD patients in three double-blind, randomized conditions: "defined Off," 60 Hz STN DBS and 130 Hz STN DBS. An improvement in aerodynamic speech parameters during 60 Hz STN DBS was accompanied by significant clinical benefit. Chronic treatment with low-frequency STN DBS may have a beneficial impact on dysarthropneumophonia, even in advanced PD patients.
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In this issue, Foltynie and colleagues2 demonstrate that patients with the met allele of the brain derived neurotrophin factor (BDNF) have an increased risk of developing LIDs earlier (see page 141). They previously investigated the link... more
In this issue, Foltynie and colleagues2 demonstrate that patients with the met allele of the brain derived neurotrophin factor (BDNF) have an increased risk of developing LIDs earlier (see page 141). They previously investigated the link between BDNF val66met polymorphism and ...