Milestone Papers

Scientific Panels Submissions

Milestone Papers in Neurology

The section of the Milestone Papers in Neurology will highlight those publications that have changed the way we think about, understand, diagnose or treat neurological diseases and conditions.

You can find below a list of Milestone Papers in Neurology, recommended by the EAN Scientific Panels.

EAN Scientific Panels

Title of Publication of Milestone PaperThe reason why this paper was selectedLink
European Resuscitation Council and European Society of Intensive Care Medicine Guidelines 2021: Post-resuscitation care.Latest guidelines from the European societies of Resuscitation and Intensive Care on the acute management of comatose patientsLink
European Academy of Neurology guideline on the diagnosis of coma and other disorders of consciousnessEuropean guidelines on diagnostic methods for patients with disorders of consciousness, elaborated by a workgroup of this Scientific PanelLink
Practice guideline update recommendations summary: Disorders of consciousness: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology; the American Congress of Rehabilitation Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation ResearchLatest guidelines elaborated by a consortium of American Societies on the care of patients with disorders of consciousnessLink
Detection of Brain Activation in Unresponsive Patients with Acute Brain Injury

This is the milestone paper because it is dedicated to the new term in the sphere of DoC - covert cognition and how it can be detected with the help of EEG and its analysis by machine learning.Link
Therapies to Restore Consciousness in Patients with Severe Brain Injuries: A Gap Analysis and Future Directions

For the first time knowledge gap analysis in all five therapeutic classes for patients with DoC was performed with a suggestion of a precision medicine approach in order to address these gaps.Link
Risk factors for 2-year mortality in patients with prolonged disorders of consciousness: An international multicentre studyThe international multicentre prospective study devoted to the evaluation of  2-year mortality rate and its bedside predictors (feasible multimodal assessmennt)Link
Title of Publication of Milestone PaperThe reason why this paper was selectedLink
Comparison of carbamazepine, phenobarbital, phenytoin and primidone in partial and secondarily generalized tonic-clonic seizures.This is the milestone paper because it represents the first-in-time evidence class I comparative trial of antiseizure medication treatment. Never again such a methodologiocal masterpiece was published.Link
Presurgical evaluation of epilepsyThis is the most comprehensive and still valid review article and thus the best possible introduction into the concept and methodology of presurgical epilepsy diagnostics.Link
Early identification of refractory epilepsyThis is an all-time citation classic. The study prospectively followed the success of antiseizure medications and revealed that refractoriness can be diagnosed much earlier than previously suggested.Link


Title of Publication of Milestone PaperThe reason why this paper was selectedLink
Action recognition in the premotor cortexPerception and action are core components of human behavior. In this work, the authors recorded the electrical activity of monkeys’ premotor cortex neurons. The activation of these neurons had been primarily associated with action performance. Remarkably, the authors found a subset triggered not only when the monkeys performed a specific action, but also when they observed one experimenter performing similar actions. These neurons were called "mirror neurons". Their existence in the human brain was later uncovered. These results greatly advanced our understanding of the unified mechanisms of action-perception and emotion-related behaviors.Link
Navigation-related structural change in the hippocampi of taxi driversAuthors studied healthy adults working as taxi drivers in London and showed that:  a) their posterior hippocampi were larger than matched controls and b) that hippocampi volume increase was related with the years of practice as taxi drivers. A previous work, with functional brain imaging, showed the activation of the posterior hippocampus in mental tasks related to navigation, thus corroborating the participation of the posterior hippocampi in this function. The work is creative, ecological and demonstrates the effect of environmental stimulation on brain structure in human adults. The latter was a breakthrough in conceptual and empirical knowledge at the time.Link
Dorsal and ventral streams: a framework for understanding aspects of the functional anatomy of languageThe authors propose a dual loop model of language organization, based on an evolutionary perspective and on the main cortico-subcortical pathways connecting the anterior and posterior language regions. The ventral pathway supports the mapping of sound to meaning making an interface with the semantic system while the dorsal pathway, lateralized to the left hemisphere, maps sound to the articulatory representations, underlying the processing of phonology and syntax. The model is simple, includes the classical language areas and the subcortical fiber tracts connecting them. It explains the pattern of language disorder that can be found following different brain lesions.Link
Awareness impairment in Alzheimer’s disease and frontotemporal dementia: a systematic MRI reviewThis review aims to define awareness impairment and related disturbances in neurodegenerative diseases, including Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) spectrum of disorders. This systematic review highlights the importance of awareness impairment and related domains in neurodegenerative disorders, especially in AD and FTLD, and it outlines MRI structural and functional correlates in these populations.Link


Title of Publication of Milestone PaperThe reason why this paper was selectedLink
Community-acquired bacterial meningitisIt is an important paper on bacterial meningitis.Link


Title of Publication of Milestone PaperThe reason why this paper was selectedLink

The Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy



Title of Publication of Milestone PaperThe reason why this paper was selectedLink
Diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease: International MOGAD Panel proposed criteriaSeveral antibody-mediated diseases affecting the CNS have been recently recognized as distinct conditions which enter the differential diagnosis with MS. These include aquaporin-4 seropositive neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Histopathologic, clinical, laboratory and imaging features are significantly different among these conditions. Also treatment and prognosis are diverse. This urges the development and application of diagnostic criteria which are specific for these conditions. This consensus paper, from an International Panel of experts, proposes diagnostic criteria for MOGAD in which the presence of MOG-IgG is a core criterion. A validation of these criteria is now required.Link


Title of Publication of Milestone PaperThe reason why this paper was selectedLink
Primary stroke prevention worldwide: translating evidence into actionStroke is the second most common cause of death and third leading cause of disability, creating a rapidly growing public health burden. Despite the available knowledge about primary stroke prevention, current strategies are partially implemented and inadequately effective, while the reasons underlying this important gap are multifactorial and poorly understood. This Health Policy paper based on a multifaceted methodology, provides a critical situational evaluation of current primary prevention strategies and guidelines, economic analysis, identification of facilitators and barriers for implementation, and evidence-based pragmatic solutions for primary stroke prevention, highlighting the emerging value of the involvement of multiple stakeholders (healthcare professionals, policy makers, patients, funders).Link
Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019Updated epidemiological evidence (incidence, prevalence, risk factors, mortality, disability) on stroke is of paramount importance for the planning of evidence-based stroke strategies. This proposed paper, based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), presents standardized epidemiological estimates for stroke for 204 countries and territories from 1990 to 2019. Stroke cases and deaths because of stroke were substantially increased especially in low-income countries, although age-standardized rate reductions were observed especially for those >70 years. The fastest-growing risk factor was high body-mass index. Therefore, the urgent need for effective implementation of primary prevention strategies for stroke is highlighted.Link


Title of Publication of Milestone PaperThe reason why this paper was selectedLink
Accelerated Brain Volume Loss Caused by Anti-β-Amyloid Drugs: A Systematic Review and Meta-analysisImmunomodulatory drugs targeting amyloid-beta brain depositions are on the cusp becoming a game-changer for the therapy of early stages of Alzheimer’s disease. At the same time, there is a substantial controversy among specialists and in the public eye about various aspects of treatment, benefits, and adverse effects. Here, Alves et al. provide a systematic review and meta-analytical evidence (8062 < n < 10279) for anti-amyloid beta therapy-induced accelerated hippocampus and whole-brain atrophy. Similarly, ARIA-inducing monoclonal antibodies accelerated brain atrophy, demonstrated by increased ventricular volume. The authors interpret their findings in the context of therapy-related negative impact on brain health.       Link


Title of Publication of Milestone PaperThe reason why this paper was selectedLink
Diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease: International MOGAD Panel proposed criteriaMOGAD or MOG Antibody-Associated Disease is a recently recognized disease entity that differs from MS and NMOSD. Presence of anti-MOG antibodies is crucial in the diagnosis. These international consensus criteria will need to be validated in the coming years, may help  to identify patients with MOGAD and will be useful in research and clinical trials investigating novel therapeutic approaches.Link


Title of Publication of Milestone PapeThe reason why this paper was selectedLINK
Radiotherapy plus concomitant and adjuvant temozolomide for glioblastomaThe phase III trial that demonstrated the survival benefit of the addition of temozolomide to radiotherapy in newly diagnosed glioblastomas, establishing the current standard of treatmentLink
An integrated genomic analysis of human glioblastoma multiformeThe first identification of recurrent IDH mutations in gliomasLink
Vorasidenib in IDH1- or IDH2-Mutant Low-Grade GliomaThe phase III trial that first demonstrated the utility of IDH inhibition in treatment-naïve IDH mutant low-grade gliomasLink


Title of Publication of Milestone PaperThe reason why this paper was selectedLink
2022 American College of Rheumatology/EULAR classification criteria for giant cell arteritisThe diagnosis of giant cell arteritis (GCA) with ultrasonography is one of the best examples of how this technique adds accuracy to the diagnosis, quickly and non-invasively, allowing a timely treatment intervention. This paper shows that diagnostic criteria of GCA have greater sensitivity then before, mainly due to the input of the ultrasonography. Its hallmark is the halo sign, a homogenous, hypoechoic artery wall thickening; this inflammatory thickening is non-compressible, where we can press it with the probe, as in the temporal arteries. Depending on the clinical setting, a non-compressible halo sign may replace the need for temporal artery biopsy.Link


Title of Publication of Milestone PaperThe reason why this paper was selectedLink
The course of the terminal phase in patients with amyotrophic lateral sclerosis. Journal of Neurology 2001; 248: 612-616.One of the first european pubblications opening to the role of palliative care in neurologyLink
Motor neurone disease: a hospice perspective. Br Med J, 1992. 304(6825): 471-3.The first evidence of involvement of ALS patients in palliative careLink
Oliver DJ, Borasio GD, Caraceni A, de Visser M, Grisold W, Lorenzl S, Veronese S, Voltz R.
A consensus review on the development of palliative care for patients with chronic and progressive neurological disease.  Eur J Neurol 2016;23: 30-38.
The first joint publication between EACP and EAN, a consensus document on the role of palliative care in neurologyLink
Withdrawal of assisted ventilation at the request of a patient with motor neurone disease: guidance for professionalsThis is a seminal paper from the Association for Palliative Medicine of Great Britain and Ireland explaining how to proceed with withdrawals of life sustaining treatmentsLink
The role of palliative care in patients with neurological diseases. Nature Neurology 2013; 9: 292-295.This is a complete review of the role of palliative care in neurological conditionsLink
Neuropalliative care. Priorities to move the field forward. Neurology 2018; 91: 217-226.It describes the growht of neuropalliative care as a sub medical specialty and how to best integrate it into neurological pathways of care.Link
Pace A, Dirven L, Koekkoek JAF et al. European Association for Neuro-Oncology (EANO) guidelines for palliative care in adults with glioma. The Lancet Oncology 2017; 18: e330-340.European guidelines on palliative care in brain tumorsLink
Veronese S, Gallo G, Valle A, Cugno C, Chio A, Calvo A, Cavalla P, Zibetti M, Rivoiro C, Oliver DJ. Specialist palliative care improves the quality of life in advanced neurodegenerative disorders: Ne-PAL, a pilot randomized controlled study. BMJ Supp Pall Care 2017; 7: 164-172. One of the first trials showing benefit of palliative care in neurodegenerative conditionsLink
Solari A, Giordanoa A, Sastre-Garriga J, Kopke S, Rahn AC, Kleiter I, Aleksovska K, Battaglia MA, Bay J, Copetti M, Drulovic J, Kooij L, Mens J, Meza Murillo ER, Milanov I, Milo R, Pekmezovic T, Vosburgh J, Silber E, Veronese S, Patti F, Voltz R, Oliver D on behalf of the guideline task force. EAN guideline on palliative care of people with severe, progressive multiple sclerosis. European Journal of Neurology 2020; 27: 1510-1529EAN guidelines on palliative care in multiple sclerosisLink
Kluger BM, Hudson P,  Hanson LC,  Bužgová R, Creutzfeldt CJ,  Gursahani R, Sumrall  M, White C, Oliver  DJ, Pantilat SZ, Miyasaki J.  Palliative care to support the needs of adults with neurological disease. Lancet Neurol 2023; 22: 619–31. Recent review of the evidence of the impact of palliative care in neurological conditions and priorities for education and researchLink