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  • Comment |

    Despite the development of many new anti-seizure drugs over the past two decades, around one-third of individuals with epilepsy are without effective treatment. This pharmacoresistance is poorly understood, but new treatments targeting epileptogenesis instead of seizures have shown potential in animal models and are now being translated into the clinic.

    • Holger Lerche
  • Comment |

    Following extensive progress in the treatment of relapsing multiple sclerosis, the major challenge in the field is now to develop effective therapies for progressive forms of multiple sclerosis. As the first signs of success emerge, now is the time to consider the research needed to move the field forward.

    • Alan Thompson
    •  & Olga Ciccarelli
  • Comment |

    The introduction of therapies for spinal muscular atrophy (SMA) has rapidly changed the clinical landscape, transforming SMA from a lethal to a treatable disease. This transformation has driven further advances, from population screening imperatives to novel treatment delivery approaches, while uncovering health disparities and fuelling debate regarding drug pricing.

    • Michelle A. Farrar
    •  & Matthew C. Kiernan
  • Comment |

    Despite the strong treatment effects of mechanical thrombectomy in acute ischaemic stroke, penumbral tissue loss before recanalization and ischaemia–reperfusion injury after diminish functional outcomes and call for adjunct treatments. Classical neuroprotection strategies could consequently be revived, but novel treatment targets are also emerging through mechanistic research.

    • Guido Stoll
    •  & Mirko Pham
  • Comment |

    Despite negative findings from numerous clinical trials of potential disease-modifying therapies for Alzheimer disease, amyloid remains the most compelling therapeutic target. Advances in biomarker methods now enable accurate monitoring of Alzheimer disease progression from the earliest stages of the disease. We must therefore redouble efforts to find an effective treatment.

    • Michael S. Rafii
    •  & Paul S. Aisen
  • Comment |

    In current usage, ‘concussion’ describes a clinical presentation, but does not identify the underlying pathological process and therefore cannot be considered a true diagnosis. However, mounting evidence indicates diffuse axonal injury as a likely pathological substrate for concussion, thereby providing a framework to develop true diagnostic criteria.

    • Douglas H. Smith
    •  & William Stewart
  • Comment |

    After going virtual, the European Academy of Neurology 2020 Congress became the biggest neurology meeting in history. The overarching theme was ‘Time for action: predict, prevent, repair’ — three upcoming Reviews in Nature Reviews Neurology, written by speakers at the congress, highlight the importance of the theme across neurology.

    • Anthony G. Marson
    •  & Claudio L. A. Bassetti
  • Comment |

    The importance of reported neurological manifestations of coronavirus disease 2019 (COVID-19) is still unclear. Nevertheless, an immediate and ongoing neurological challenge posed by the COVID-19 pandemic is the management of patients who are undergoing immunotherapy for existing neuroimmunological disease.

    • Hans-Peter Hartung
    •  & Orhan Aktas
  • Comment |

    Trials of aducanumab in Alzheimer disease were previously discontinued following a phase III futility analysis, but Biogen now says that additional data indicate that longer exposure to the higher dose might be effective. The company is seeking FDA approval for the treatment; however, the limited data released do not establish efficacy.

    • Robert Howard
    •  & Kathy Y. Liu
  • Comment |

    The FDA approvals of siponimod and cladribine for secondary progressive multiple sclerosis raise questions about the diagnostic criteria for multiple sclerosis phenotypes and their applicability to clinical trials. A simpler classification for the disease could be the answer.

    • Navid Manouchehri
    •  & Olaf Stüve
  • Comment |

    Inflammatory processes contribute to neurological disorders, and many therapeutic breakthroughs in neurological disease have been immune-targeted. The choice of neuroinflammation as the theme for the 5th European Academy of Neurology Congress in 2019 and of this Focus issue highlights its importance to neurologists across the discipline.

    • Nils Erik Gilhus
    •  & Günther Deuschl
  • Comment |

    In the march towards disease-modifying treatments for Alzheimer disease, immunotherapy with antibodies against amyloid-β protein is furthest along in human trials. The news that Biogen’s aducanumab showed no cognitive benefit in phase III trials requires careful analysis of what went wrong and how to position anti-amyloid agents among other therapeutic approaches.

    • Dennis J. Selkoe
  • Comment |

    Stroke has been misplaced in the International Classification of Disease (ICD) since 1955, but is now classed as a neurological disease in the new ICD-11. The reclassification required a bureaucratic struggle between clinicians and the World Health Organization, but will bring great benefits.

    • Raad Shakir
  • Comment |

    The treatment of multiple sclerosis (MS) has evolved remarkably over the past 25 years. This progress has been enabled by advances in research, drug development and active engagement of the scientific community with regulatory authorities. However, an inconsistent approach to MS disease courses could have a negative impact on the drug development process.

    • Timothy Coetzee
    •  & Alan J. Thompson