The Lancet Neurology

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[Editorial] A radical proposal for the EU budget: brain health

Every day, the European Parliament in Brussels, Belgium, bustles with the activity of meetings held by lobbyists trying to influence decision-making. But now that the European Union (EU) is negotiating the Multiannual Financial Framework for the 2021–27 budget, the frenzy seems even more intense. The European Brain Council (an umbrella organisation of scientific and professional societies, patient organisations, and industry partners with an interest in mental and neurological health) did not neglect this window of opportunity and, on Feb 18, 2020, hosted an event at the European Parliament entitled “Brain Health as a Global Priority—time for the EU to act now”.

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[Comment] Old and new breakthroughs in neuromyelitis optica

More than a decade ago, the identification of a disease-specific antibody targeting the aquaporin 4 (AQP4) water channel on astrocytes opened a new chapter in neuroimmunology: neuromyelitis optica, up to then classified as a rare clinical variant of multiple sclerosis, emerged as an independent entity in clinical practice. The AQP4 antibody transformed our understanding of the underlying disease mechanisms, of possible treatment targets, and disease phenomenology. The biomarker enabled better characterisation of patient cohorts1 and paved the way for the definition of neuromyelitis optica spectrum disorder (NMOSD), with the AQP4 antibody at the core of a new set of diagnostic criteria.

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[Comment] Rethinking multiple sclerosis treatment strategies

The landscape of multiple sclerosis treatment has substantially evolved over the past few years following the approval and commercialisation of several new drugs. Based on the mechanisms of action and efficacy and safety profiles of these drugs, for most patients one of two treatment approaches is normally used. The first approach, which focuses on safety, is escalation, and starts with lower risk disease-modifying therapies shifting to higher risk treatment if disease activity occurs. The second approach, which prioritises efficacy, is induction, in which a strong immune intervention is used from diagnosis of disease.

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[Comment] Nusinersen in adults with spinal muscular atrophy: new challenges

Little evidence exists on the use of nusinersen in adults, as the few cohorts that have been studied were relatively small and heterogeneous.1–4

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[Comment] New paradigms of clinical trial design for genetic prion diseases

Diagnosis of a genetic, incurable disease can be devastating for affected individuals and their families. In case of genetic prion disease, a rare disease of the CNS caused by mutations of the human prion protein gene, PRNP, mutation carriers usually do not exhibit symptoms until late adulthood. Genetic prion diseases comprise a relatively small fraction (10–15%) of all prion diseases, the most common being sporadic Creutzfeldt-Jakob disease.1 Since no therapy exists except palliation, individuals with family history of genetic prion disease face the dilemmatic decision of whether to undergo genetic testing.

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[Comment] T cells in Alzheimer's disease: space invaders

Historically, neurons have been the focus of Alzheimer's disease research because neuronal loss is associated with clinical manifestions of the disease. But evidence from genetic, clinical, and experimental studies1 shows that the immune system—most notably its innate axis—also contributes to Alzheimer's disease. However, this is only one part of the story. Tony Wyss-Coray and colleagues report in Nature2 that the adaptive immune system can also have a role.

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[Correspondence] Safety of adjunctive treatment with cenobamate in patients with uncontrolled focal seizures

Krauss and colleagues1 recently published the results of a trial of adjunctive treatment with cenobamate (YKP3089) for uncontrolled focal seizures. In this trial, 437 patients with focal seizures refractory to at least one antiepileptic drug were randomly assigned to placebo (n=108) or to three different adjunctive cenobamate dose groups (108 patients to 100 mg per day, 110 to 200 mg per day, and 111 to 400 mg per day). Of the 437 patients, 138 (32%) were taking lamotrigine, 122 (28%) were on carbamazepine, and 64 (15%) were taking oxcarbazepine.

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[Correspondence] Safety of adjunctive treatment with cenobamate in patients with uncontrolled focal seizures – Authors' reply

We agree with Mudigoudar and Wheless. Cenobamate is generally well tolerated, but some patients can develop dizziness, drowsiness, and other CNS-related symptoms when cenobamate is titrated rapidly to high doses (usually >200 mg per day) in combination with treatment with high doses of sodium channel modulators. Cenobamate is approved to be titrated slowly over 11 weeks to 200 mg per day, which usually mitigates pharmacodynamic interactions. The titration schedule used in our clinical trial referenced by Mudigoudar and Wheless was much quicker (weekly titration).

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[Corrections] Correction to Lancet Neurol 2020; 19: 234–46

Armangue T, Olivé-Cirera G, Martínez-Hernandez E, et al. Associations of paediatric demyelinating and encephalitic syndromes with myelin oligodendrocyte glycoprotein antibodies: a multicentre observational study. Lancet Neurol 2020; 19: 234–46—In figure 1 of this Article, 239 patients were incorrectly reported to have confirmed acute disseminated encephalomyelitis. These patients had confirmed acquired demyelinating syndrome. This correction has been made to the online version as of March 18, 2020, and will be made to the printed version.

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[Corrections] Correction to Lancet Neurol 2020; 19: 247–54

Hopfner F, Höglinger GU, Kuhlenbäumer G, et al. β-adrenoreceptors and the risk of Parkinson's disease. Lancet Neurol 2020; 19: 247–54—In this Rapid Review the sentence from the summary originally stated “β-adrenoceptor antagonists are used by billions of patients with neurological disorders, primarily for the treatment of migraine and action tremor (mainly essential tremor), worldwide.” This has been rewritten and is now “According to current treatment guidelines, more than a billion patients with neurological disorders have an indication for the use of β-adrenoceptor antagonists (mainly migraine and essential tremor)”.

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