Alain Destée

Centre Hospitalier Régional Universitaire de Lille · Movement Disorders Unit

We describe excessive buccal saliva (EBS) prevalence in patients with Parkinson’s Disease (PD) and controls of the COPARK study, its changes between “ON” and OFF” conditions and over time, its impact on Health-related Quality of life (HRQoL), and factors associated with this condition. We studied 671 ambulatory PD patients and 177 age/sex-matched c...

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...

The original version of this article unfortunately contained a mistake in Fig. 2 caption.

Background Subthalamic nucleus deep brain stimulation (STN-DBS) has demonstrated its efficacy on motor complications in advanced Parkinson's disease (PD) but does not modify disease progression. Genetic forms of PD have been associated with different cognitive progression profiles. Objective To assess the effect of PD-related genetic mutations on...

Introduction Immediate-release (IR) amantadine has been marketed for Parkinson’s disease (PD) therapy for 50 years, while two novel extended-release formulations have only recently reached the market in the US. Objectives The aim of this study was to describe amantadine IR utilization patterns in the French COPARK cohort, at baseline and after 2 y...

Leucine-rich repeat kinase 2 is a promising therapeutic target for the treatment of Parkinson's disease, and orally bioavailable, brain penetrant and highly potent LRRK2 kinase inhibitors are in early stages of clinical testing. Detection of LRRK2 phosphorylation, as well as phosphorylation of Rab10, a LRRK2 kinase substrate, have been proposed as...

Background: The frequency of late-onset Huntington's disease (>59 years) is assumed to be low and the clinical course milder. However, previous literature on late-onset disease is scarce and inconclusive. Objective: Our aim is to study clinical characteristics of late-onset compared to common-onset HD patients in a large cohort of HD patients fr...

Parkinson’s disease is a progressive neurodegenerative disorder characterized by loss of dopaminergic neurons, pathological accumulation of alpha-synuclein and motor symptoms, but also by non-motor symptoms. Metabolic abnormalities including body weight loss have been reported in patients and could precede by several years the emergence of classica...

Parkinson’s disease (PD) is a progressive movement neurodegenerative disease associated with a loss of dopaminergic neurons in the substantia nigra of the brain. Oxidative stress, a condition that occurs due to imbalance in oxidant and antioxidant status, is thought to play an important role in dopaminergic neurotoxicity. Nicotinamide adenine dinuc...

Background and objectives: Studies assessing the correlations between L-DOPA-induced dyskinesias (LIDs) and motor fluctuations with Health-related Quality of Life (HRQoL) in Parkinson's Disease (PD) have yielded conflicting results. This study aimed at assessing the relationship between LIDs and motor fluctuations with HRQoL in PD patients, and to...

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify...

Background: In Huntington's Disease (HD) cognitive decline can occur before unequivocal motor signs become apparent. As cognitive decline often starts early in the course of the disease and has a progressive nature over time, cognition can be regarded as a key target for symptomatic treatment. The specific progressive profile of cognitive decline...

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify...

CAG triplet expansions in Ataxin-2 gene (ATXN2) cause spinocerebellar ataxia type 2 and have a role that remains to be clarified in Parkinson's disease (PD). To study the molecular events associated with these expansions, we sequenced them and analyzed the transcriptome from blood cells of controls and three patient groups diagnosed with spinocereb...

The gastro-intestinal peptide ghrelin has been assigned many functions. These include appetite regulation, energy metabolism, glucose homeostasis, intestinal motility, anxiety, memory or neuroprotection. In the last decade, this pleiotropic peptide has been proposed as a therapeutic agent in gastroparesis for diabetes and in cachexia for cancer. Gh...

Purpose To better define the clinical characteristics of idiopathic oromandibular dystonia, we studied voice, speech, and swallowing disorders and their impact on activities of daily living. Method Fourteen consecutive patients with idiopathic oromandibular dystonia and 14 matched, healthy control subjects were included in the study. Results Dysa...

Autosomal-recessive early-onset parkinsonism is clinically and genetically heterogeneous. The genetic causes of approximately 50% of autosomal-recessive early-onset forms of Parkinson disease (PD) remain to be elucidated. Homozygozity mapping and exome sequencing in 62 isolated individuals with early-onset parkinsonism and confirmed consanguinity f...

Protein synthesis is a fundamental process to gene expression impacting diverse biological processes notably adaptation to environmental conditions. The initiation step, which involves the assembly of the ribosomal subunits at the mRNA initiation codon, involved initiation factor including eIF4G1. Defects in this rate limiting step of translation a...

This study aimed at determining the prevalence of falling in PD patients, to assess generic and disease-specific clinical and pharmacological factors, relationship with health-related quality of life (HR-QoL) and changes in falls from OFF to ON in patients with motor fluctuations. Six-hundred and eighty-three PD patients of the COPARK survey were e...

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 therefor...

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 n...

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...

Importance Freezing of gait (FOG) is a common axial symptom of Parkinson disease (PD).Objective 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.Design,...

Background: 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. Objective: To identify predictive factors for the efficacy of low-...

Background 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 objectiv...

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 as...

Most available pattern recognition methods in neuroimaging address binary classification problems. Here, we used relevance vector machine (RVM) in combination with booststrap resampling ('bagging') for non-hierarchical multiclass classification. The method was tested on 120 cerebral (18)fluorodeoxyglucose (FDG) positron emission tomography (PET) sc...

Aims: The pathophysiological role of iron in Parkinson's disease (PD) was assessed by a chelation strategy aimed at reducing oxidative damage associated with regional iron deposition without affecting circulating metals. Translational cell and animal models provided concept proofs and a delayed-start (DS) treatment paradigm, the basis for prelimin...

Even with optimal dopaminergic treatments, many patients with Parkinson's disease (PD) are frequently incapacitated by apathy prior to the development of dementia. We sought to establish whether rivastigmine's ability to inhibit acetyl- and butyrylcholinesterases could relieve the symptoms of apathy in dementia-free, non-depressed patients with adv...

AFQ056 is a novel, selective metabotropic glutamate receptor 5 antagonist. This was a 13-week, double-blind, placebo-controlled study. Patients with Parkinson's disease and moderate-to-severe levodopa (l-dopa)-induced dyskinesia who were receiving stable l-dopa/anti-parkinsonian treatment and were not currently receiving amantadine were randomized...

Impulse control disorder is a well-known complication of dopaminergic treatment of Parkinson's disease. Pathological gambling, compulsive sexual behavior, compulsive buying and binge eating disorders are the most common features of this disorder. We present two cases of kleptomania in association with dopaminergic treatment for two patients with Pa...

The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently, we identified the V471A polymorphism in the autophag...

The catechol-O-methyltranferase (COMT) is one of the main enzymes that metabolise dopamine in the brain. The Val158Met polymorphism in the COMT gene (rs4680) causes a trimodal distribution of high (Val/Val), intermediate (Val/Met) and low (Met/Met) enzyme activity. We tested whether the Val158Met polymorphism is a modifier of the age at onset (AAO)...

The role of genetic factors in Parkinson's disease has been demonstrated by the discovery of chromosomal loci associated with the disease and genes responsible for Mendelian forms. Among autosomal-dominant forms, the genes SNCA and LRRK2 are formally associated with the disease. SNCA gene plays a central role in the pathogenesis of the disease and...

Objective: The AMANDYSK trial was designed to assess long-term efficacy of chronic treatment with amantadine in patients with Parkinson disease (PD) and levodopa-induced dyskinesia (LID). Methods: This was a 3-month, multicenter, randomized, double-blind, placebo-controlled, parallel-group, wash-out study conducted in 57 amantadine-treated (≥200...

Background: In view of freezing of gait's circumstances of occurrence in Parkinson's disease, attentional resources appear to be involved in step initiation failure. Anticipatory postural adjustments (APAs) are essential because they allow unloading of the stepping leg and so create the conditions required for progression. Our main objective was t...

Background Given that memantine is thought to decrease N-methyl-D-aspartic-acid-related (NMDA) glutamatergic hyperactivity and improve locomotion in rats, we sought to assess the drug's impact on axial symptoms in advanced Parkinson's disease (PD). Methods We performed a 90-day, randomised, double-blind, study with two parallel arms: 20 mg/day mem...

Mutations in the spastic paraplegia 7 (SPG7) gene encoding paraplegin are responsible for autosomal recessive hereditary spasticity. We screened 135 unrelated index cases, selected in five different settings: SPG7-positive patients detected during SPG31 analysis using SPG31/SPG7 multiplex ligation-dependent probe amplification (n = 7); previously r...

High-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) has been shown to reduce akinesia in Parkinson's disease (PD). Given that the processing of sensory afferents is deficient in PD and might be involved in akinesia, we sought to determine whether or not the application of very HF rTMS [intermit...

Despite optimum medical management, many patients with Parkinson's disease are incapacitated by gait disorders including freezing of gait. We aimed to assess whether methylphenidate--through its combined action on dopamine and noradrenaline reuptake--would improve gait disorders and freezing of gate in patients with advanced Parkinson's disease wit...

Introduction.– La présence d’une dysarthrie hypokinétique et de troubles de la déglutition a largement été décrite à un stade évolué de la maladie de Parkinson mais peu à la phase précoce. Objectifs.– L’objectif de notre étude était d’évaluer la sévérité des différentes composantes de la dysarthrie, ainsi que la déglutition chez 26 patients parkin...

The selection of task-relevant information requires both the focalization of attention on the task and resistance to interference from irrelevant stimuli. Both mechanisms rely on a dorsal frontoparietal network, while focalization additionally involves a ventral frontoparietal network. The role of subcortical structures in attention is less clear,...

Introduction Impulse control disorders (ICDs) in Parkinson's disease (PD) are associated with dopamine agonist treatment. Although discontinuation of dopamine agonist is recommended, ICD management has not been precisely stated. The aims of the study were to describe demographic and clinical characteristics in a group of PD patients with ICDs and t...

Rationnel Le très grand bénéfice des deux traitements pivots dans la Maladie de Parkinson (MP) que sont la L-dopa et la stimulation subthalamique sont mis en péril à long terme par l’apparition de troubles axiaux avec des freezing de la marche (FOG). Ceux-ci pourraient être en partie liés à une déplétion dopaminergique et noradrénergique dans les b...

Impulse control disorders (ICDs) in Parkinson's disease (PD) are associated with dopamine agonist treatment. Although discontinuation of dopamine agonist is recommended, ICD management has not been precisely stated. The aims of the study were to describe demographic and clinical characteristics in a group of PD patients with ICDs and to evaluate th...

Background Given that memantine is thought to decrease N-methyl-D-aspartic-acid-related (NMDA) glutamatergic hyperactivity and improve locomotion in rats, we sought to assess the drug's impact on axial symptoms in advanced Parkinson's disease (PD). Methods We performed a 90-day, randomised, double-blind, study with two parallel arms: 20 mg/day mema...