A5049389628- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Advanced Neuroimaging Techniques and Applications
- Advanced MRI Techniques and Applications
- Parkinson's Disease Mechanisms and Treatments
- Neurological disorders and treatments
- Mind wandering and attention
- Atomic and Subatomic Physics Research
- Medical Imaging Techniques and Applications
- Psychological Well-being and Life Satisfaction
- Neurological and metabolic disorders
- Cerebral Palsy and Movement Disorders
- Lanthanide and Transition Metal Complexes
- Epilepsy research and treatment
- Amyotrophic Lateral Sclerosis Research
- Metabolism and Genetic Disorders
- Ion Transport and Channel Regulation
- Cardiovascular Syncope and Autonomic Disorders
- Neurogenetic and Muscular Disorders Research
- Lysosomal Storage Disorders Research
- Bone and Joint Diseases
- Radiomics and Machine Learning in Medical Imaging
- Advanced NMR Techniques and Applications
- Connective tissue disorders research
- Adenosine and Purinergic Signaling
Sorbonne Université
2014-2025
Centre National de la Recherche Scientifique
2014-2025
Resonance Research (United States)
2015-2025
University of Minnesota
2015-2025
Institut du Cerveau
2014-2025
Inserm
2014-2025
Assistance Publique – Hôpitaux de Paris
2015-2024
University of Minnesota System
2022
Nantes Université
2022
Forschungszentrum Jülich
2022
To determine whether neurochemical concentrations obtained at two MRI sites using clinical 3T scanners can be pooled when a highly optimized, nonvendor short-echo, single-voxel proton MRS pulse sequence is used in conjunction with identical calibration and quantification procedures.A modified semi-LASER (TE = 28 ms) was to acquire spectra from brain regions (cerebellar vermis pons) on Siemens the same B0 B1 protocols different cohorts of healthy volunteers (N 24-33 per site) matched for age...
As gene-based therapies may soon arise for patients with spinocerebellar ataxia (SCA), there is a critical need to identify biomarkers of disease progression effect sizes greater than clinical scores, enabling trials smaller sample sizes.We enrolled unique cohort SCA1 (n = 15), SCA2 12), SCA3 20) and SCA7 10) 24 healthy controls similar age, sex body mass index. We collected longitudinal imaging data at baseline follow-up (mean interval months). performed both manual automated volumetric...
Based on our previous work in Huntington disease (HD) showing improved energy metabolism muscle by providing substrates to the Krebs cycle, we wished obtain a proof-of-concept of therapeutic benefit triheptanoin using functional biomarker brain validated HD.We performed an open-label study (31)P magnetic resonance spectroscopy (MRS) measure levels phosphocreatine (PCr) and inorganic phosphate (Pi) before (rest), during (activation), after (recovery) visual stimulus. We MRS 10 patients at...
On the basis of our previous work with triheptanoin, which provides key substrates to Krebs cycle in brain, we wished assess its therapeutic effect patients glucose transporter type 1 deficiency syndrome (GLUT1-DS) who objected or did not tolerate ketogenic diets.We performed an open-label pilot study three phases 2 months each (baseline, treatment and withdrawal) eight GLUT1-DS (7-47 years old) non-epileptic paroxysmal manifestations. We used a comprehensive patient diary record motor...
Spinocerebellar ataxias (SCAs) belong to polyglutamine repeat disorders and are characterized by a predominant atrophy of the cerebellum pons. Proton magnetic resonance spectroscopy ((1) H MRS) using an optimized semiadiabatic localization adiabatic selective refocusing (semi-LASER) protocol was performed at 3 T determine metabolite concentrations in cerebellar vermis pons cohort patients with SCA1 (n=16), SCA2 (n=12), SCA3 (n=21), SCA7 (n=12) healthy controls (n=33). Compared controls,...
Spinocerebellar ataxia type 7 (SCA7) is a retinal-cerebellar degenerative disorder caused by CAG-polyglutamine (polyQ) repeat expansions in the ataxin-7 gene. As many SCA7 clinical phenotypes occur mitochondrial disorders, and magnetic resonance spectroscopy of patients revealed altered energy metabolism, we considered role for dysfunction. Studies mice uncovered marked impairments oxygen consumption respiratory exchange. When examined cerebellar Purkinje cells mice, observed network...
Neurofilament light chain (NfL) is a marker of brain atrophy and predictor disease progression in rare diseases such as Huntington Disease, but also more common neurological disorders Alzheimer's disease. The aim this study was to measure NfL longitudinally autosomal dominant spinocerebellar ataxias (SCAs) establish correlation with clinical imaging parameters. We enrolled 62 pathological expansions carriers (17 SCA1, 13 SCA2, 19 SCA3, SCA7) age-matched controls prospective biomarker between...
The growing number of modalities (e.g. multi-omics, imaging and clinical data) characterizing a given disease provides physicians statisticians with complementary facets reflecting the process but emphasizes need for novel statistical methods data analysis able to unify these views. Such sets are indeed intrinsically structured in blocks, where each block represents set variables observed on group individuals. Therefore, classical tools cannot be applied without altering their organization,...
Friedreich ataxia (FRDA) is an autosomal recessive with no approved treatments. Leriglitazone a selective peroxisome proliferator-activated receptor γ agonist that crosses the blood-brain barrier and, in preclinical models, improved mitochondrial function and energy production. We assessed effects of leriglitazone patients FRDA proof-of-concept study.In this double-blind, randomized controlled trial, eligible participants (age 12-60 years) had genetically confirmed FRDA, Scale for Assessment...
Spinocerebellar ataxia type 2 (SCA2) is a rare, inherited neurodegenerative disease characterized by progressive deterioration in both motor coordination and cognitive function. Atrophy of the cerebellum, brainstem, spinal cord are core features SCA2; however, evolution pattern whole-brain atrophy SCA2 remain unclear. We undertook multisite, structural magnetic resonance imaging (MRI) study to comprehensively characterize neurodegeneration profile SCA2. Voxel-based morphometry analyses 110...
Objective We aimed to quantify differences in the brain and spinal cord between Friedreich ataxia controls, stratified by age disease stage, including for first time young children. Methods TRACK‐FA is largest prospective, longitudinal, multi‐modal neuroimaging study date. assessed individuals with 5 42 years, at 7 sites across 4 continents. The 17 imaging primary outcome measures (POMs) were selected from metrics that showed a significant longitudinal change previous small‐scale studies....
Friedreich ataxia is a progressive neurodegenerative disorder characterized by cerebellar and spinal atrophy. However, studies to elucidate the longitudinal progression of pathology in brain are somewhat inconsistent limited, especially for early-stage ataxia. Using multimodal neuroimaging protocol, combined with advanced analysis methods, we sought identify macrostructural microstructural alterations patients better understand its distribution patterns progression. We enrolled 28 20 age-...
Niemann-Pick type C (NPC) disease is a lysosomal storage disorder characterized by wide clinical spectrum and non-specific conventional magnetic resonance imaging (MRI) signs. As substrate reduction therapy with miglustat now used in almost all patients, its efficacy the course of are sometimes difficult to evaluate. Neuroimaging biomarkers could prove useful this matter. We first performed retrospective analysis volumetric diffusion tensor (DTI) data on 13 adult NPC patients compared...
Development of imaging biomarkers for rare neurodegenerative diseases such as spinocerebellar ataxia (SCA) is important to non-invasively track progression disease pathology and monitor response interventions. Diffusion MRI (dMRI) has been shown identify cross-sectional degeneration white matter (WM) microstructure connectivity between healthy controls patients with SCAs, using various analysis methods. In this paper, we present dMRI data in SCAs type 1, 2, 3, 6 matched controls, including...
Spinal cord damage is a hallmark of Friedreich's ataxia (FRDA), but its progression and clinical correlates remain unclear.
The main culprit gene for paroxysmal kinesigenic dyskinesia, characterized by brief and recurrent attacks of involuntary movements, is PRRT2. location the primary dysfunction associated with dyskinesia remains a matter debate may vary depending on etiology. While striatal has often been implicated in these patients, evidence from preclinical models indicates that cerebellum could also play role. We aimed to investigate role pathogenesis PRRT2-related humans.We enrolled 22 consecutive...
Based on the hypothesis of a brain energy deficit, we investigated safety and efficacy triheptanoin paroxysmal episodes in patients with alternating hemiplegia childhood due to ATP1A3 mutations. We conducted randomized, double-blind, placebo-controlled crossover study triheptanoin, at target dose corresponding 30% daily calorie intake, ten Each treatment period consisted 12-week fixed-dose phase, separated by 4-week washout period. The primary outcome was total number events. Secondary...
Abstract Friedreich ataxia is the most common hereditary ataxia. Atrophy of spinal cord one hallmarks disease. MRI and magnetic resonance spectroscopy are powerful non-invasive tools to investigate pathological changes in cord. A handful studies have reported cross-sectional alterations using diffusion MRI. However, our knowledge no longitudinal MRI, or MRS results been Here, we investigated early-stage cervical ataxia, a multimodal protocol comprising morphometric (anatomical MRI),...
Introduction Drug development for neurodegenerative diseases such as Friedreich’s ataxia (FRDA) is limited by a lack of validated, sensitive biomarkers pharmacodynamic response in affected tissue and disease progression. Studies employing neuroimaging measures to track FRDA have thus far been their small sample sizes follow up. TRACK-FA, longitudinal, multi-site, multi-modal natural history study, aims address these shortcomings enabling better understanding underlying pathology identifying...
Abstract Objective Spinocerebellar ataxia type 2 (SCA2) is a rare, inherited neurodegenerative disease characterised by progressive deterioration in both motor coordination and cognitive function. Atrophy of the cerebellum, brainstem, spinal cord are core features SCA2, however evolution pattern whole-brain atrophy SCA2 remain unclear. We undertook multi-site, structural magnetic resonance imaging (MRI) study to comprehensively characterize neurodegeneration profile SCA2. Methods Voxel-based...
The striatum is a well‐known region affected in Huntington disease (HD). However, other regions, including the visual cortex, are implicated. We have identified previously an abnormal energy response cortex of patients at early stage HD using 31 P magnetic resonance spectroscopy ( MRS). therefore sought to further characterize these metabolic alterations with 1 H MRS well‐validated semi‐localized by adiabatic selective refocusing (semi‐LASER) sequence that allows measurement expanded number...
Abstract Huntington’s disease (HD) is a monogenic, fully penetrant neurodegenerative disorder. Widespread white matter damage affects the brain of patients with HD at very early stages disease. Fixel-based analysis (FBA) novel method to investigate contribution individual crossing fibers and detect possible alterations in both fiber density fiber-bundle morphology. Diffusion-weighted magnetic resonance spectroscopy (DW-MRS), on other hand, quantifies motion metabolites vivo, thus enabling...