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Sommaires des Revues - The Lancet Neurology

The Lancet Neurology


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[Editorial] Treating rare disorders: time to act on unfair prices  Voir?

The first disease-modifying treatment for spinal muscular atrophy (SMA), nusinersen, was approved by the US Food and Drug Administration (FDA) on Dec 23, 2016, and by the European Medicines Agency (EMA) on May 30, 2017. The approval was based on evidence of clinically meaningful improvements in motor milestones in young children with varying degrees of disease severity from two clinical trials (ENDEAR, NCT02193074, and CHERISH, NCT02292537). The regulatory approval is a historic development, but it is unlikely that the drug will be available to all patients who would benefit from treatment, unless its manufacturer offers a fairer price than the current cost of this drug.

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[Comment] NOR-TEST-ing tenecteplase in acute ischaemic stroke  Voir?

Despite the transformational impact of endovascular treatment on patients with acute ischaemic stroke from proximal cerebral artery occlusion, thrombolysis with intravenous alteplase remains the mainstay of reperfusion therapy because it is widely available and the standard of care upon which the evidence for endovascular treatment has been based.1 However, because alteplase has well recognised limitations, including reduced efficacy in large clots, risk of major intracranial haemorrhage, and requirement for a continuous infusion, there is an imperative to continue efforts to find more efficient, more effective, and safer lytic treatment in acute ischaemic stroke.

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[Comment] Imaging neuroinflammation to monitor α-synucleinopathy  Voir?

Neuroinflammation in neurodegenerative diseases generally refers to a chronic immune response in the CNS, in which innate immune cells such as microglia and astrocytes are responsible for robust inflammatory responses and neuronal death. However, each neurodegenerative disease also has a preclinical period, during which potentially harmful inflammatory events might already be happening. With the advent of disease-modifying drugs, early detection of abnormal signals from the brain milieu during the preclinical phase is important because diagnostic symptoms, once developed, are so relentless that few therapeutic countermeasures are left for clinicians to use.

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[Comment] Unravelling neurodegeneration in multiple sclerosis  Voir?

Neurodegeneration is postulated to be a major contributor to neurological disability in multiple sclerosis and might be the dominant process underlying progressive multiple sclerosis. Whether neurodegeneration is an independent process in patients with multiple sclerosis or its occurrence is secondary to inflammation remains unknown.1 Current therapies, focused on immune modulation, are generally less effective in the progressive forms than in the relapsing remitting forms of the disease. Therefore, understanding neurodegeneration might be fundamental to determining how to prevent neurological disability in all patients with multiple sclerosis, but especially in those in whom a progressive disease course dominates.

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[Comment] Traumatic brain injury: an enduring challenge  Voir?

The outcomes of traumatic brain injury (TBI) can vary widely from no lasting effects to devastating and persistent consequences. Detailed understanding of the sequelae of TBI has been limited by the heterogeneity of this disorder and, until recently, there have been few studies of long-term outcomes in particular. However, recent progress in characterising specific consequences and the availability of longitudinal studies of outcomes are providing the basis for improved understanding of TBI sequelae, as highlighted in two Series papers on TBI in The Lancet Neurology.

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[Comment] A new era of multiple sclerosis rehabilitation: lessons from stroke  Voir?

Just over 20 years ago, no treatments were available for multiple sclerosis, a disease characterised by two overlapping processes of nervous system injury: inflammatory destruction of myelin and neurodegeneration of grey and white matter.1 Disease-modifying drugs, particularly the new oral medications, have changed the prognosis of multiple sclerosis, contributing to increased periods of disease stability and greater potential for rehabilitative therapies to reduce impairment.2 In The Lancet Neurology, Robert Motl and colleagues3 argue that exercise can be a beneficial rehabilitation strategy for people with multiple sclerosis, but that three limitations obstruct translation of exercise research into practice: the quality and scope of the evidence, the need for improved understanding of the mechanisms underlying the beneficial effects of exercise, and the need for a framework and toolkit for knowledge translation.

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[Comment] T cells and Parkinson's disease  Voir?

Although effector and regulatory T-cell populations can promote either neurotoxic or neuroprotective effects in the control of the brain's microenvironment, how these cells are induced during Parkinson's disease is not known.1,2 David Sulzer and colleagues3 have reported a functional role of α-synuclein in immune tolerance. The authors posit that lymphocyte populations emerge from α-synuclein induction of autoreactive CD4+ and CD8+ T cells.

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[Corrections] Corrections  Voir?

Pointing the way to primary prevention of dementia. Lancet Neurol 2017; 16: 677. In this Editorial, the website for World Wide FINGERS was incorrect and should have been http://wwfingers.com/. This correction has been made to the online version as of Sept 12, 2017.
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[Correspondence] Edaravone for treatment of early-stage ALS  Voir?

The Edaravone (MCI-186) ALS 19 Study Group1 reported on the safety and efficacy of edaravone in a phase 3 study of patients with early-stage amyotrophic lateral sclerosis. The primary endpoint was change in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) scores from baseline to 24 weeks after randomisation. Before randomisation, patients entered a 12-week observation period, and those patients with a decrease in ALSFRS-R score of 1–4 points were randomly assigned to receive edaravone or placebo.

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[Correspondence] Edaravone for treatment of early-stage ALS – Authors' reply  Voir?

We thank Jesús Mora for allowing us to provide clarifications on our study.1 The protocol2 required all investigators to receive ALSFRS-R video training and to be certified to meet the same evaluation standards. One patient's ALSFRS-R score at cycle 2 was evaluated by an investigator who did not meet this standard, and this cycle 2 score was therefore excluded from analyses. Nonetheless, since the cycle 6 endpoint data were available and adequate, this exclusion did not affect our primary analysis.

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[Correspondence] Obesity and the nervous system: more questions  Voir?

In their Review, Phillipe O'Brien and colleagues1 concluded that, although extensive data exist to indicate that obesity—a component of the metabolic syndrome—is a mediator of CNS and peripheral nervous system (PNS) injury, the ideal intervention to prevent the associated cognitive impairment, autonomic neuropathy, and polyneuropathy is not yet known.

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[Correspondence] Obesity and the nervous system: more questions  Voir?

In their excellent Review, Phillipe O'Brien and colleagues1 describe the neurological consequences of obesity. However, the authors did not mention migraine, which is a common, chronic, disabling neurological disorder.2 Epidemiological research shows a link between migraine and obesity that is further substantiated by putative pathophysiological mechanisms.3 A body of evidence supports a role for adipokines (such as leptin, adiponectin, interleukin 6, and TNF-α, among others), which are mediators of inflammatory processes, in the onset, persistence, and progression of migraines.

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[Correspondence] Obesity and the nervous system: more questions – Authors' reply  Voir?

We appreciate the insightful comments pertaining to our Review1 on the neurological consequences of obesity. Our Review focused on the increasing medical literature supporting an association between obesity and CNS and peripheral nervous system (PNS) injury. Several observational and intervention studies have provided consistent evidence substantiating a potential causal link. The two letters raise important issues pertaining to the strength of the current evidence for other associations involving obesity and CNS outcomes.

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[In Context] David Menon: the incredible, incurable, clinical rationalist  Voir?

“I have this urge to find explanations, and I can't seem to get rid of it”, confesses David Menon, Professor of Anaesthesia at University of Cambridge (Cambridge, UK), referring to his Twitter profile that neatly labels him as an incurable clinical rationalist. Menon suggests that, for him, evidence alone is not quite enough; “why have we got this result—this is the question that consumes me”, he explains. There is something particularly reassuring about a doctor who is a self-confessed knowledge-addict—this may well be the essence of Menon.

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[In Context] Ed Wild  Voir?

Ed Wild is a Medical Research Council clinician scientist and principal research associate at University College London (UCL, London, UK). He studied medicine at Cambridge University (Cambridge, UK) and did his PhD at UCL. His research, including the multinational HDClarity study, focuses on studying human biofluids to develop biomarkers to help test innovative therapies for Huntington's disease.

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[In Context] Gian Lorenzo Bernini's 17th century white noise machine  Voir?

For centuries, people have sought relief from insomnia through a wide assortment of methods. Studies in young adults and children, which investigated non-pharmacological approaches in sleep induction, found that white noise triggered sleep and reduced night-waking behaviours.1–2 Nowadays, different kinds of white noise devices are available for insomnia relief, which can sound like rushing waterfalls or wind blowing through trees. It is less well known that one of the most ancient insomnia treatment machines—which used the principles of white noise—was invented in the 17th century by the illustrious architect and sculptor Gian Lorenzo Bernini (1598–1680), known for designing the Fountain of the Four Rivers (Rome, Italy), and the colonnades of St.

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[In Context] Biomarkers, bioprediction, and ethics  Voir?

“Foresight! Foresight!, which takes us ceaselessly beyond ourselves and often places us where we shall never arrive.” This quote by Jean-Jacques Rousseau appears on the opening page of Matthew L. Baum's book The Neuroethics of Biomarkers. Rousseau pinpoints the problem physicians are constantly grappling with, when trying to synthesise medical history, clinical signs, and results from investigations to make a diagnosis and ultimately a prognosis, and decide the interventions that may best serve our patients.

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[In Context] Keeping an open mind in neurological practice  Voir?

A J Lees' Mentored by a Madman is a kaleidoscopic mix of his experiences as a neurologist, his private passions and how they have informed his career, as well as his thoughts regarding some of the bureaucracy that limits research and medical practice today. What gives this book such a unique perspective is the part played by the titular “madman”—William Burroughs, author of iconic novels such as Junky and Naked Lunch. It is a rare thing to find a book with such a unique perspective and accompanying content; however, this is exactly what Mentored by a Madman provides.

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[In Context] Perspectives on time  Voir?

You are able to recall the past, imagine the future, and count the passing seconds. Our ability to tell time deserves all the marvel we usually reserve for our other cognitive faculties. Human beings have been telling time for at least as long as we have been able to foresee the advantage that crafting a tool today will bring tomorrow. Whilst it is true that certain members of our extended family in the animal kingdom are able to anticipate future events—jays, for example, demonstrate a remarkable awareness of their food's coming expiry date—human beings undoubtedly possess unrivalled timekeeping abilities.

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[In Context] An outsider's journey in brain science  Voir?

Robert Newman's Neuropolis is an ambitious attempt to provide the layman with a survival guide to current “brain science”, as he terms it. He argues that “brainless interpretations of brain science are…giving us a dehumanising and pessimistic picture of ourselves”, and that this interpretation is based less on science and more on so-called philosophical stowaways. Professionally, Newman is a comedian; his book stems from his interest in neuroscience and is based on his own research. As a self-proclaimed outsider, he presents a potentially unique insight into the field.

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[Articles] Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): a phase 3, randomised, open-label, blinded endpoint trial  Voir?

Tenecteplase was not superior to alteplase and showed a similar safety profile. Most patients enrolled in this study had mild stroke. Further trials are needed to establish the safety and efficacy in patients with severe stroke and whether tenecteplase is non-inferior to alteplase.
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[Articles] Assessment of neuroinflammation in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a case-control study  Voir?

In patients with IRBD, increased microglial activation was detected by PET in the substantia nigra along with reduced dopaminergic function in the putamen. Further studies, including more participants than were in this study and longitudinal follow-up, are needed to support our findings and evaluate whether the presence of activated microglia in patients with IRBD represents a marker of short-term conversion to a clinically defined synucleinopathy in the near future.

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[Articles] Retinal layer segmentation in multiple sclerosis: a systematic review and meta-analysis  Voir?

The largest and most robust differences between the eyes of people with multiple sclerosis and control eyes were found in the peripapillary RNFL and macular GCIPL. Inflammatory disease activity might be captured by the INL. Because of the consistency, robustness, and large effect size, we recommend inclusion of the peripapillary RNFL and macular GCIPL for diagnosis, monitoring, and research.

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[Series] The chronic and evolving neurological consequences of traumatic brain injury  Voir?

Traumatic brain injury (TBI) can have lifelong and dynamic effects on health and wellbeing. Research on the long-term consequences emphasises that, for many patients, TBI should be conceptualised as a chronic health condition. Evidence suggests that functional outcomes after TBI can show improvement or deterioration up to two decades after injury, and rates of all-cause mortality remain elevated for many years. Furthermore, TBI represents a risk factor for a variety of neurological illnesses, including epilepsy, stroke, and neurodegenerative disease.

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[Review] Prediction of motor recovery after stroke: advances in biomarkers  Voir?

Stroke remains a leading cause of adult disability, and the recovery of motor function after stroke is crucial for the patient to regain independence. However, making accurate predictions of a patient's motor recovery and outcome is difficult when based on clinical assessment alone. Clinical assessment of motor impairment within a few days of stroke can help to predict subsequent recovery, while neurophysiological and neuroimaging biomarkers of corticomotor structure and function can help to predict both motor recovery and motor outcome after stroke.

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[Review] Therapies targeting DNA and RNA in Huntington's disease  Voir?

No disease-slowing treatment exists for Huntington's disease, but its monogenic inheritance makes it an appealing candidate for the development of therapies targeting processes close to its genetic cause. Huntington's disease is caused by CAG repeat expansions in the HTT gene, which encodes the huntingtin protein; development of therapies to target HTT transcription and the translation of its mRNA is therefore an area of intense investigation. Huntingtin-lowering strategies include antisense oligonucleotides and RNA interference targeting mRNA, and zinc finger transcriptional repressors and CRISPR-Cas9 methods aiming to reduce transcription by targeting DNA.

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[Personal View] Exercise in patients with multiple sclerosis  Voir?

Exercise can be a beneficial rehabilitation strategy for people with multiple sclerosis to manage symptoms, restore function, optimise quality of life, promote wellness, and boost participation in activities of daily living. However, this population typically engages in low levels of health-promoting physical activity compared with adults from the general population, a fact which has not changed in the past 25 years despite growing evidence of the benefits of exercise. To overcome this challenge, the main limitations to promoting exercise through the patient–clinician interaction must be addressed.

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Dernière mise à jour : 19/09/2017 : 18:53


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