Publications by authors named "Pierre Francois Pradat"

Background And Objectives: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease leading to the loss of motor function and muscle strength. Nonpharmacologic neuromodulative therapeutic approaches such as active exercise may contribute to preserve motor functions in ALS, but this hypothesis remains debated. The present meta-analysis first aimed to evaluate the effect of active exercise on function and muscle strength preservation.

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Changes in Hoffmann reflex (H-reflex) exhibit heterogeneity among patients with amyotrophic lateral sclerosis (ALS), likely due to phenotype diversity. Current knowledge primarily focuses on soleus H-reflex, which may demonstrate an initial increase before subsequent decline throughout the disease course. The main objective was to investigate other muscles, to determine whether H-reflex changes could be associated with patient phenotype (onset site, functional disabilities).

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  • ALS is a disease that affects nerve cells and usually leads to severe muscle problems and a short life expectancy of 3-5 years.
  • The study explored how cholesterol and its levels in muscle might relate to the problems caused by ALS, showing that ALS patients had more cholesterol in their muscles.
  • Researchers noticed that certain genes related to cholesterol movement were overactive in ALS patients, suggesting that cholesterol buildup might be linked to the severity of their muscle issues.
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Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive loss of motor neurons. The limited efficacy of recent therapies in clinical development may be linked to lack of drug penetration to the affected motor neurons due to the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB).

Methods: In this work, the safety and efficacy of repeated short transient opening of the BSCB by low intensity pulsed ultrasound (US, sonication) was studied in females of an ALS mouse model (B6.

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Amyotrophic lateral sclerosis (ALS) is a rare multisystem neurodegenerative disease leading to death due to respiratory failure. Riluzole was the first disease modifying treatment approved in ALS. Randomized clinical trials showed a significant benefit of riluzole on survival in the months following randomization, with a good safety profile.

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  • Amyotrophic lateral sclerosis (ALS) primarily affects motor areas of the brain and spinal cord, but this study investigates less understood cerebellar involvement which may worsen symptoms like speech and balance issues.
  • The research involved 113 healthy individuals and 212 ALS patients, focusing on specific genetic groups, to assess changes in cerebellar structure and connectivity over time using advanced neuroimaging techniques.
  • Findings revealed significant reductions in certain cerebellar regions and connectivity impairments in ALS patients, particularly those with sporadic forms of the disease, highlighting the cerebellum's role in the progression of ALS symptoms.
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  • Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease leading to muscle weakness and respiratory issues, and arimoclomol has shown potential neuroprotective effects in animal studies.
  • The ORARIALS-01 trial was a multicenter, double-blind study that assessed the safety and efficacy of arimoclomol in ALS patients, involving random assignment to either the drug or a placebo.
  • A total of 245 patients participated, and the primary goal was to evaluate treatment outcomes over 76 weeks, analyzing both efficacy and safety data among the participants.
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Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, characterized by the death of upper (UMN) and lower motor neurons (LMN) in the motor cortex, brainstem, and spinal cord. Despite decades of research, ALS remains incurable, challenging to diagnose, and of extremely rapid progression. A unifying feature of sporadic and familial forms of ALS is cortical hyperexcitability, which precedes symptom onset, negatively correlates with survival, and is sufficient to trigger neurodegeneration in rodents.

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  • - Thoracic disc herniation is rare, making up less than 1% of spinal herniations, and while often asymptomatic, it can lead to spinal cord ischemia.
  • - A case involving a 43-year-old man showed Brown-Sequard syndrome, where spinal cord ischemia was linked to a thoracic disc extrusion, initially not compressing the cord on MRI.
  • - The patient was treated conservatively, and after a few months, he recovered as the disc extrusion decreased on its own, illustrating the complexities in diagnosis and management of this condition.
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Background: Studies showed the impact of sex and onset site (spinal or bulbar) on disease onset and survival in ALS. However, they mainly result from cross-sectional or survival analysis, and the interaction of sex and onset site on the different proxies of disease trajectory has not been fully investigated.

Methods: We selected all patients with repeated observations in the PRO-ACT database.

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Purpose Of Review: Although neuroimaging in motor neuron diseases (MNDs) continues to generate important novel academic insights, the translation of novel radiological protocols into viable biomarkers remains challenging.

Recent Findings: A multitude of technological advances contribute to the success of academic imaging in MND such as the availability of high-field MRI platforms, novel imaging techniques, quantitative spinal cord protocols to whole-brain spectroscopy. International collaborations, protocol harmonization efforts, open-source image analysis suites also fuel developments in the field.

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  • Spinal cord stimulation (SCS) is being researched not just for chronic pain relief, but also for its potential to restore function after spinal cord injuries.
  • Advances in understanding spinal cord lesions and new technologies in neuroengineering are leading to innovative SCS strategies, like spatiotemporal neuromodulation, which enables targeted stimulation during movements.
  • Combining SCS with intensive rehabilitation methods is crucial for effectiveness, and there’s a pressing need for comprehensive clinical trials to evaluate these approaches for safety and effectiveness.
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Background: Motor capacity is crucial in amyotrophic lateral sclerosis (ALS) clinical trial design and patient care. However, few studies have explored the potential of multimodal MRI to predict motor capacity in ALS. This study aims to evaluate the predictive value of cervical spinal cord MRI parameters for motor capacity in ALS compared to clinical prognostic factors.

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  • ALS (amyotrophic lateral sclerosis) is a common and fatal motor neuron disease in adults, with recent research providing new insights after years of challenges and failures in treatment.
  • A literature search from January 2016 to June 2022 indicates advancements in early diagnosis, monitoring, and treatment options for ALS.
  • Despite its incurable nature, there is growing optimism regarding ALS management and outcomes for patients in the near future.
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Amyotrophic lateral sclerosis (ALS) is an extremely heterogeneous disease of motor neurons that eventually leads to death. Despite impressive advances in understanding the genetic, molecular, and pathological mechanisms of the disease, the only drug approved to date by both the FDA and EMA is riluzole, with a modest effect on survival. In this opinion view paper, we will discuss how to address some challenges for drug development in ALS at the conceptual, technological, and methodological levels.

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Mutations in profilin 1 (PFN1) have been identified in rare familial cases of Amyotrophic Lateral Sclerosis (ALS). PFN1 is involved in multiple pathways that could intervene in ALS pathology. However, the specific pathogenic role of PFN1 mutations in ALS is still not fully understood.

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This study retrospectively compared all-cause and cause-specific mortality in French male professional football players with data from France's national population. Altogether, 6114 individuals born in Metropolitan France or in one of its overseas territories who played at least one competitive match in France's professional football championships between January 1, 1968 and December 31, 2015, were identified and followed up for vital status obtained from a national reference database until December 31, 2015. Data on all-cause and cause-specific mortality were subsequently compared to the expected number of deaths for the national population after standardization for the year, age, and sex.

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Background: The functional reorganization of brain networks sustaining gait is poorly characterized in amyotrophic lateral sclerosis (ALS) despite ample evidence of progressive disconnection between brain regions. The main objective of this fMRI study is to assess gait imagery-specific networks in ALS patients using dynamic causal modeling (DCM) complemented by parametric empirical Bayes (PEB) framework.

Method: Seventeen lower motor neuron predominant (LMNp) ALS patients, fourteen upper motor neuron predominant (UMNp) ALS patients and fourteen healthy controls participated in this study.

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Amyotrophic lateral sclerosis is a relentlessly progressive multi-system condition. The clinical picture is dominated by upper and lower motor neuron degeneration, but extra-motor pathology is increasingly recognized, including cerebellar pathology. Post-mortem and neuroimaging studies primarily focus on the characterization of supratentorial disease, despite emerging evidence of cerebellar degeneration in amyotrophic lateral sclerosis.

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Extracellular vesicles can mediate communication between tissues, affecting the physiological conditions of recipient cells. They are increasingly investigated in Amyotrophic Lateral Sclerosis, the most common form of Motor Neurone Disease, as transporters of misfolded proteins including SOD1, FUS, TDP43, or other neurotoxic elements, such as the dipeptide repeats resulting from expansions. EVs are classified based on their biogenesis and size and can be separated by differential centrifugation.

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Background: The cause of the motor neuron (MN) death that drives terminal pathology in amyotrophic lateral sclerosis (ALS) remains unknown, and it is thought that the cellular environment of the MN may play a key role in MN survival. Several lines of evidence implicate vesicles in ALS, including that extracellular vesicles may carry toxic elements from astrocytes towards MNs, and that pathological proteins have been identified in circulating extracellular vesicles of sporadic ALS patients. Because MN degeneration at the neuromuscular junction is a feature of ALS, and muscle is a vesicle-secretory tissue, we hypothesized that muscle vesicles may be involved in ALS pathology.

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  • The study evaluates a theoretical index, called the postural instability discrimination index (PI), for assessing postural instability in amyotrophic lateral sclerosis (ALS).
  • Key biomechanical factors influencing postural instability were identified, specifically the backward displacement of the pressure center (APA) and the active vertical braking of the mass center (Braking-index), which were incorporated into the PI formula.
  • The PI demonstrated strong discriminatory performance with high sensitivity (90.91%) and specificity (83.87%), indicating its potential as a reliable clinical tool for personalized assessment of postural instability in ALS patients.
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